Brain Ponderings podcast with Mark Mattson
Conversations with neuroscientists, neurologists, evolutionary biologists, anthropologists, computer scientists, and others that ponder the brain. Here are a few of the questions that BRAIN PONDERINGS will tackle: How have brains evolved to enable success in diverse environments? How does the brain develop in the womb and in early life? What are the mechanisms responsible for learning and memory, language, and emotions? How does the brain respond to life’s challenges? In what ways does the brain influence the body and vice-versa? What is known about the causes of psychiatric, neurodegenerative, and other brain disorders? What new technologies are being developed to treat neurological disorders? How do naturally occurring and man-made chemicals affect the brain? How can gene therapy, cell regeneration, and brain stimulation be used for brain disorders? What are the boundaries between ethical and unethical neuroscience research?
info_outline
Roshan Cools: Dopamine’s Roles in Cognitive Control, Motivation, Decision-Making, ADHD, and PD
03/06/2025
Roshan Cools: Dopamine’s Roles in Cognitive Control, Motivation, Decision-Making, ADHD, and PD
Dopamine is best known as a neurotransmitter involved in the experiencing of pleasure and reward, and for its role in addiction to drugs, gambling, food, etc. But dopamine is also very important in the brain’s ability to evaluate computational tradeoffs (cost versus benefit) and make decisions. In this episode Roshan Cools a Professor of cognitive neuropsychiatry at Radbout University in the Netherlands talks about how dopamine normally controls the neuronal circuits in the striatum and prefrontal cortex that regulate motivation and cognitive control. By combining PET imaging to measure relative dopamine release with various cognitive control tasks and administration of drugs such as methylphenidate (Ritilin) that affect dopamine signaling she found that every individual has their own dopamine ‘set point’. She talks about how dopaminergic drugs enhance cognitive control in ADHD patients but impair cognitive control in patients with Parkinson’s disease. We also talk about potential pharmacological and behavioral modifications to optimize cognitive control in healthy people. LINKS Professor Cools web page: https://www.roshancools.com/ Chemistry of the adaptive mind: https://www.cell.com/action/showPdf?pii=S0896-6273%2819%2930838-4 Dopamine’s role in making cost versus benefit decisions: https://pmc.ncbi.nlm.nih.gov/articles/PMC8282630/pdf/nihms-1697802.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/35558670
info_outline
Maryanne Garry: Misinformation, Disinformation, False Memories, AI, and Our Future
03/03/2025
Maryanne Garry: Misinformation, Disinformation, False Memories, AI, and Our Future
In this episode I talk with Professor Maryanne Garry at the University of Waikato New Zealand about several interrelated realms of human cognition that are fundamental to changes in the behaviors of individuals and social groups as influenced by electronic media and artificial intelligence. Dr. Garry has devoted her career to understanding how memories of one’s past experiences can be distorted, how false information can become engrained in one’s system of beliefs. She talks about individual and collective memories, and the brain’s source monitoring systems and how they are influenced by group identity, repetition of information (whether true or not). Interestingly although memories of untruths can be retracted when new information is provided they can still influence one’s decision-making. She also talks about how social media and AI (LLMs) influence the brain’s source monitoring systems and potential approaches to ameliorating their adverse effects on mental health and societal discord. LINKS Dr. Garry’s lab webpage: https://www.garrylab.com/ Collective and autobiographical memories: https://www-tandfonline-com.proxy1.library.jhu.edu/doi/epdf/10.1080/09658211.2022.2154804 Retracted memories: https://pmc.ncbi.nlm.nih.gov/articles/PMC9365748/pdf/13421_2022_Article_1328.pdf LLMs and the institutionalization of misinformation: https://pdf.sciencedirectassets.com/271877/1-s2.0-S1364661323X00138/1-s2.0-S1364661324002213/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEG4aCXVzLWVhc3QtMSJGMEQCIA9kHgyXdZwhJDF2Nc6gQiDwWhuj%2F9fvysEcbyMKnaM8AiBEX6%2BAkbxOT%2FT%2FJCTkVCeOnibe%2Fin%2BeiHRN8auAjLO7yq8BQin%2F%2F%2F%2F%2F%2F%2F%2F%2F%2F8BEAUaDDA1OTAwMzU0Njg2NSIMnDX%2Bz%2BiS%2BD9b8%2BsCKpAFlPWcxi2Nu4wg%2FlKU8mSVoZQPyiR6LQkJokbH6TlJvixjI04Sd92Kj5SSAHB8QvzpkbIuJoErUOjgSlkpGTlKK7kMqkMt2S%2FSmUyp5OzH5PlhGyxSi3Lpq%2Bdjol9vmiF9rXTEeHeRrHzUh48X4HajvARh9q6lC6v%2FCSx84dpolcD3kMlhYIEuYfJbVc%2Fm4k%2F9xtjX2NtA3BhLHFs8nzUuuDcNtLxZ3mi7SLbQz9oBGMdeJFd2bBjf%2ByCpjqUl%2Bs9ALlI75kYC1aDPdB2f84XWB78f9CKz%2FtNob%2FjKE9tMcwB3Dni8%2FtndhQRjybd74siNn2sApJu%2FXKwgKsqJEvKP8CDYYTgnSVrRAseqXSdLKoA63G91ZG9K7nOjODivQI%2BpzciLPlvzYVjpeEJ5LE3PC5VVYxCkOQKUtwDvUgXigGtfHsgazln3m8WMBxakhHXrKEWK7q%2FuxuLBle%2BD%2BK%2FdM1aw2JpS7hyllAgfZ4cuSBexwzQ%2B3OjGg4Fe2MBdTmpa0ZG9WT7B7KNo2FxoiKEZJupQ3z%2FaMOIBCMCqa0EvuMCQpIqZKS8zxngNpJeOVpTuWv%2BJ3EQjM3T6GL9hxNA%2BszUz7MR7KN6so2RZvU32fCtHB14j2vHVXkaytDu653flfPWASPWQKprXowbOsghYz0UegMyUjO1a67axaYcTUrVAt7OxvM%2BwyZDkSPJhOWHDfcSyL30v%2BhTLjWxGRy4GdrEndVdgAw3RmjDWx0E4CrmUkycwWQND01xhJI6IijMO%2BgoJ%2FFVSnrNNvGVGCCtU80%2FylVKonMGKTDptdPrqsi8aQDdQYdyL5sq4itFXa6Obi0EvBTjlB8p%2BMORusgVwSP9PBJFbLLbT%2FnxegI2FJJ0wh5%2BMvgY6sgFhGU%2FH5TGFnQMV5o1J5r37XL5V8jHthF%2FO3kUtL%2Fk6oDRUfFYPQxvyRxi0EzFaGcDu7jYC53O%2BZxrzPgPJS1qP6%2BNJu6%2FDls8iyGvg3JAi85RLRRgZlhp3wnfLghXW4W6VnmXzQzMUdjCahckzzB9w8XVmhGrXw%2F4JIvHgSx73D6oVy%2BPMi4h%2F4I5T08ApqPSaR7bkrnYvAtWgfjRynIpiabV%2BBisHSuNwL11EsBTf3auq&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250301T144026Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTY4USPLILK%2F20250301%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=03ec372fac008431242909cb94e0acfca84a8a7d4fdc142df102bf78149b9761&hash=1da48c96274cce2ef2914eaf9bd37a118e05e359da92f349fb5c1a767dcd852e&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S1364661324002213&tid=spdf-52d87662-932c-46b0-925b-296bc39e2460&sid=f0d8a6a836dc5742e59bb5900fc7ac98a3f4gxrqa&type=client&tsoh=d3d3LXNjaWVuY2VkaXJlY3QtY29tLnByb3h5MS5saWJyYXJ5LmpodS5lZHU%3D&rh=d3d3LXNjaWVuY2VkaXJlY3QtY29tLnByb3h5MS5saWJyYXJ5LmpodS5lZHU%3D&ua=0f105a505f56585c0053&rr=919968d1f9843b0b&cc=us
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/35511535
info_outline
Michal Schwartz: How Immune System Cells Promote Brain Health and Recovery From Damage
02/25/2025
Michal Schwartz: How Immune System Cells Promote Brain Health and Recovery From Damage
It had long been thought that the brain was ‘immunologically privileged’ (physically separated from the immune system). However, this dogma was overturned by a series of discoveries including those made by Professor Michal Schwartz at the Weizmann Institute. In this episode I talk with Michal about the different types of immune cells that are located in ‘immunological niches’ of the brain (choroid plexus, perivascular space, meninges..) and how these cells play critical roles in maintaining normal brain health and function (neurogenesis, synaptic plasticity, learning and memory). In addition, Michal tells us how the immune system is vital for healing and protecting the brain in case of injury or disease in a process called protective autoimmunity. LINKS The Schwartz laboratory webpage: https://www.weizmann.ac.il/brain-sciences/labs/schwartz/ Review article in Science: https://www-science-org.proxy1.library.jhu.edu/doi/epdf/10.1126/science.abo7649 Review article in Neuron: https://pdf.sciencedirectassets.com/272195/1-s2.0-S0896627324X00021/1-s2.0-S0896627324008821/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEOT%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEaCXVzLWVhc3QtMSJGMEQCIH9qI%2FHFo0TFwwhZ5hnpbny3R%2BBmGbU0Q6Jf2eSs4aMwAiAg1gQKCHXgtyB1QTOz9%2BHuFdAEwUjZfZxdN7qIuitxnSqyBQgdEAUaDDA1OTAwMzU0Njg2NSIMamYY8Czn0NEpjijeKo8Fst5HNVzMqIsK6tHRy1OPd3%2BiRf4CleOwam945epwh%2BWJCRv3vjV8cHVmcUPqNnQI6CNJ%2BHjihnNnr1KKKh25j9oqm8eVOB6EPMOQmOlZ8JnfOw82gvpFwLvNDQBspUb%2FSS7qIz1LTJRkQASLgxJzjCDB2emDLOTnwBmVrktQOqTAH1A04l%2FY5xtc1GQI9emBGMXRHjBFSH2LHORJ08vvfDEMpF%2FnFWesKWqcGC9SrZdSxXgiVvnL2kX%2FA96V1%2B5AevSLvAQz2GiAfG7IjuurqeZht68BqTv%2Bi%2BRqNRIYIFbGxDzeucq3ac1xrSlaHwznp31k%2BFLwJoLLYSEixqfBpuBat%2Ft9vzhxMlcflvyteLNaP4B4EHiuQ9DixBMYQ0hKdtHXZpd7wmY1UYM9g1S4Yc6GNMjj%2BfXQWexvCOgUbqPqIjDp4WtKdPA%2B1slxuoE4wyns%2Bvqntw01MjdbU9Bn4pBQQOwS4fzz9bFlB2iDKGAKXyN0SHqdWPpP9Scj6yJuIXOsZkSS0481ADJLyUF7n46ZFuKmYSsDdy5f5RegbcmY25YITTooTxJxK0IXBczdPZIkfWAsPvBvvq%2BREarPeOA3FAcEs5%2BOSSU41qk8QJEiHdOdnTuScsjI1yMElwnepaA8DdJ9DTU3YeXpMG7xColHHCpn%2FeCeTvP612oFVjqE4Q1yqBpdCiy2CMWdvHhtXcAZOeavgMMfqhk6OWN8qXlZubu8uFiOfDwDpPWZE5qpitKaC6pwM7lkYyecPstLn84Sh149kpVnMY1aLp2NgCZ4rvq4XWwV1dMNrPeKU7GyQBwIKIBGlQz5fHPFbINPDH8UXZW7cCe%2BT02g0BXwQY4lgzqGqxyYpe3NtS7dwzD%2B%2BO29BjqyAemqzi7IVALnQ9vlrBPSO%2BkAPcisPB%2FY%2B8BmQC16wLFwu63gufdnti8i%2FsS1H%2FD%2BpPqJ3t1vn2wie%2FOc9mgRZkY8HqNqX9Dv%2FUH%2FOICaGadyLdPc8A3sjo7bPtUV42NA5FZwBt8YiikhkCFQwzTcrHzr5fP9kN9ThQVSY1DMSTz%2BMbLmLWoolWEwLwzL9mS3qEz2mX3h%2Boec4CYuKBRgExYTH0V1dk0bfca4YMPpvgER7iA%3D&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250223T204131Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTYZTUPN5RI%2F20250223%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=59057549b15a459c579302af14796c40e5c70192d93a62b69b68c2bd3942cd8b&hash=bc06cbd441c60c0f8ee395108521ce86afe847a68e5f109544b937b88a9c473c&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S0896627324008821&tid=spdf-34e9b5cb-d1e9-4a56-8a8b-edab99b3d37e&sid=d752fa96683d9742086a083805b7d9da151bgxrqa&type=client&tsoh=d3d3LXNjaWVuY2VkaXJlY3QtY29tLnByb3h5MS5saWJyYXJ5LmpodS5lZHU%3D&rh=d3d3LXNjaWVuY2VkaXJlY3QtY29tLnByb3h5MS5saWJyYXJ5LmpodS5lZHU%3D&ua=0f105a50500e5e5d5c53&rr=916a0981a902c99d&cc=us
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/35421770
info_outline
Diego Mendoza-Halliday: How the Brain Stays on Task - Attention, Noise Filtering and Working Memory
02/18/2025
Diego Mendoza-Halliday: How the Brain Stays on Task - Attention, Noise Filtering and Working Memory
Throughout our waking hours neural networks in our brains are processing incoming information, particularly sights and sounds, integrating those inputs with stored information, making decisions, and executing responses. Staying on task requires that we attend to the details of the task while filtering out ‘noise’. In this episode I talk with Diego Mendoza-Halliday at the University of Pittsburgh about visual working memory – what it is, what neuronal circuits are involved, and how it works. His experiments involve recording of neuronal activity in prefrontal cortex and other brain regions while individuals are performing visual working memory tasks. His findings have revealed previously unknown mechanisms. He has demonstrated that attention and working memory involve different groups of neurons and has shown that throughout the cerebral cortex there is spectro-laminar motif of neuronal oscillation frequencies that appears to play an important role in working memory. This research is not only revealing how our brains process information in a seemingly effortless manner, but may also lead to new ways of improving human productivity and treating memory disorders. LINKS Mendoza-Halliday lab webpage https://www.mendoza-halliday-lab.com/ Coding of perceived and memorized visual features in the prefrontal cortex https://pmc.ncbi.nlm.nih.gov/articles/PMC5461493/pdf/ncomms15471.pdf Dissociation of neurons involved in attention and working memory https://www.cell.com/action/showPdf?pii=S0896-6273%2823%2900935-2 Spectrolaminar motif of local field power in the cerebral cortex https://pmc.ncbi.nlm.nih.gov/articles/PMC10917659/pdf/41593_2023_Article_1554.pdf Review article on working memory https://www.annualreviews.org/docserver/fulltext/psych/74/1/annurev-psych-021422-041757.pdf?expires=1739719353&id=id&accname=guest&checksum=3C2E750794D8E913C545FF401FEA62F7
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/35332740
info_outline
Thomas Hartung: Merging Brain Organoid and AI Technologies to Accelerate Basic and Applied Research
02/11/2025
Thomas Hartung: Merging Brain Organoid and AI Technologies to Accelerate Basic and Applied Research
Professor Thomas Hartung has made a major impact in biomedical research by developing and promoting alternatives to animal research. His efforts are leading to more ethical and efficient approaches to basic and applied research in the fields of environmental toxicology, drug development, and neuroscience. In this episode I talk with Thomas about two major flourishing technologies – brain organoids and artificial intelligence – and how they are being rapidly incorporated into both basic and translational research. He provides an historical perspective on the overzealous and unnecessary use of lab animals for toxicology and drug development and then delves into emerging research on ‘organoid intelligence’ and the relationships and interactions of brain organoids and AI. A very thought-provoking conversation. LINKS Organoid Intelligence webpage: https://organoidintelligence.org/ AI and alternative texting of toxins and drugs: https://www.altex.org/index.php/altex/issue/view/166 Brain Organoids and Organoid Intelligence articles https://pmc.ncbi.nlm.nih.gov/articles/PMC10013972/pdf/frai-06-1116870.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC10796793/pdf/frai-06-1307613.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/35237455
info_outline
Magdalena Götz: Direct Conversion of Astrocytes Into Neurons – Progress and Therapeutic Potential
02/04/2025
Magdalena Götz: Direct Conversion of Astrocytes Into Neurons – Progress and Therapeutic Potential
Someday it may be possible to restore neuronal networks that have been lost or damaged by brain injury or in neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. There are as many astrocytes in the human brain as there are neurons and the astrocytes generally do not die in brain injuries and neurodegenerative disorders. Professor Magdalena Götz has shown that astrocytes can be converted directly into neurons using molecular biology technologies to manipulate a few transcription factors that switch cell fate. These new neurons grow and form synapses with each other and can integrate into functional neuronal networks and may restore brain function. In this episode Dr. Götz talks about her pioneering work on cell reprogramming that holds great promise for the repair of neuronal networks damaged by trauma, a stroke, and neurodegenerative disorders. LINKS: Professor Götz publications on PubMed: https://pubmed.ncbi.nlm.nih.gov/?term=magdalena+G%C3%B6tz&sort=date&size=200 Professor Götz Wikipedia page: https://en.wikipedia.org/wiki/Magdalena_G%C3%B6tz Review article in Neuron: https://www.cell.com/action/showPdf?pii=S0896-6273%2821%2900972-7 Selected original research articles https://pmc.ncbi.nlm.nih.gov/articles/PMC11239498/pdf/41593_2024_Article_1677.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC10719094/pdf/41591_2023_Article_2644.pdf https://www.cell.com/action/showPdf?pii=S0896-6273%2819%2930693-2
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/35145635
info_outline
Antonio Di leva: Fractal Patterns and the Brain - Applications in Basic and Clinical Neuroscience
01/30/2025
Antonio Di leva: Fractal Patterns and the Brain - Applications in Basic and Clinical Neuroscience
The Euclidean geometry that we learned in our primary education concerns man-made shapes such as rectangles, triangles, and perfect circles. However the shapes of molecules, cells, and organ systems (and their dynamic changes over time) are more complex. Some biological structures exhibit fractal geometry which is defined as “shapes and patterns that appear similar at different scales” (recursive iteration). Examples of biological structures exhibiting fractal geometry include the branches and roots of trees, blood vessels, lung airways, and the dendritic arbors of neurons. In this episode I talk with Antonio Di leva a neurosurgeon and neuroscientist at Macquarie University School of Medicine about fractal geometry and its applications to basic and clinical neuroscience. Fractal structures of neural networks optimize the energy efficiency of the brain. Dr. Di leva talks about emerging applications of fractals to diagnosis and monitoring of neurological disorders, neurosurgery, neuroimaging, and computational intelligence. Fractal analyses are not limited to structures and can also be applied to studies of recursive features dynamic processes including neural network activity. LINKS Dr. Di leva’s webpage: https://mqneurosurgery.com.au/prof-antonio-di-ieva/ Book ‘The Fractal Geometry of the Brain’: https://link.springer.com/book/10.1007/978-3-031-47606-8 Review articles: https://journals-sagepub-com.proxy1.library.jhu.edu/doi/full/10.1177/1073858413513927 https://journals-sagepub-com.proxy1.library.jhu.edu/doi/full/10.1177/1073858413513928
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/35082265
info_outline
Stephan Sigrist: Dietary Spermidine, Neuroplasticity, Aging, and Brain Health
01/27/2025
Stephan Sigrist: Dietary Spermidine, Neuroplasticity, Aging, and Brain Health
Polyamines are small organic molecules that are acquired in the diet and can also be synthesized in cells. Spermidine is a polyamine that is increasingly recognized as playing important roles in counteracting aging. Foods with high amounts of spermidine include whole grains, broccoli, and natto (fermented soybeans). Professor Stephan Sigrist at the Free University of Berlin who is widely known for his fundamental contributions to understanding how specific proteins and their interactions control the rapid release and reuptake of neurotransmitters at the presynaptic active zone. In this episode I talk with Stephan about his recent fascinating discoveries that have revealed important roles for spermidine in synaptic plasticity, and brain health and resilience. Spermidine stimulates autophagy which may be required for the anti-aging effect of dietary energy restriction. He talks about the intriguing molecular mechanism by which spermidine accomplishes these feats. LINKS Sigrist lab page: https://www.bcp.fu-berlin.de/en/biologie/arbeitsgruppen/genetik/ag_sigrist/mitarbeiter/leiter/sigrist/index.html Spermidine counteracts brain aging: https://www.cell.com/action/showPdf?pii=S2211-1247%2821%2900255-2 Autophagy mediates beneficial effects of spermidine on memory during aging: https://www.nature.com/articles/nn.3512.pdf Spermidine preserves synaptic plasticity during aging: https://pmc.ncbi.nlm.nih.gov/articles/PMC5042543/pdf/pbio.1002563.pdf Spermidine, fasting and longevity: https://pmc.ncbi.nlm.nih.gov/articles/PMC11392816/pdf/41556_2024_Article_1468.pdf Clinical trial of spermidine – effects on cognition in older folks: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2792725
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/35027665
info_outline
Jon Simons: Reality Monitoring- How the Brain Distinguishes Between Imagination and Reality
01/22/2025
Jon Simons: Reality Monitoring- How the Brain Distinguishes Between Imagination and Reality
In the moment most people can readily distinguish between information that is coming into the brain from their senses and what information their brain is generating. However, when recalling information stored in the brain’s neuronal networks the ability to distinguish between what was real and what was imagined becomes more problematic. How does the brain keep track of what we actually experienced in the past and what we imagined happened? In this episode Jon Simons who is Professor of Cognitive Neuroscience at the University of Cambridge talks about his research that is elucidating the neurobiological basis of reality monitoring including which brain regions and neuronal networks are involved, individual differences in people’s reality monitoring ability, the effects of early life experiences and aging, its alterations in schizophrenia and autism, and the broader implications of this research for individuals and societies in the [mis]information age. LINKS: Professor Simon’s laboratory web page: https://www.memlab.psychol.cam.ac.uk/ Review article https://www-sciencedirect-com.proxy1.library.jhu.edu/science/article/pii/S1364661317300554 Selected original research articles https://pmc.ncbi.nlm.nih.gov/articles/PMC2292823/pdf/ukmss-1581.pdf https://www.sciencedirect.com/science/article/pii/S0010945216301745?via%3Dihub https://pmc.ncbi.nlm.nih.gov/articles/PMC4860197/pdf/10803_2016_Article_2749.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC5292760/pdf/main.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/34955075
info_outline
Keqiang Ye: From Gut to Brain – Rogue Protein Fragments in Parkinson’s and Alzheimer’s Diseases
01/08/2025
Keqiang Ye: From Gut to Brain – Rogue Protein Fragments in Parkinson’s and Alzheimer’s Diseases
In this episode Emory University and Chinese Academy of Sciences Professor Keqiang Ye talks about his fascinating and ground-breaking trail of discoveries that have revealed previously unknown mechanism responsible for the production and accumulation of damaging fragments of the APP and Tau proteins in Alzheimer’s disease (AD) and the alpha-synuclein protein in Parkinson’s disease (PD). He discovered an enzyme called AEP that cleaves Tau and alpha-synuclein into self-aggregating toxic fragments. Eliminating or disabling AEP can prevent the disease process and preserve brain function in mouse models of AD and PD. More recently, in a series of studies his laboratory has provided evidence that the generation of rogue Tau and alpha-synuclein fragments first occurs in neurons surrounding the intestines and then propagates up the vagus nerve to the brain. Moreover, his group has shown that certain species of bacteria in the gut can promote the development of the disease. Finally, Professor Ye has developed drugs that inhibit AEP or activate BDNF receptors as potential treatments for AD and PD. LINKS Key publications: https://pmc.ncbi.nlm.nih.gov/articles/PMC4224595/pdf/nihms623922.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC5315368/pdf/nihms825673.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC10482867/pdf/41467_2023_Article_41283.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC8408610/pdf/EMBJ-40-e106320.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC6951265/pdf/41422_2019_Article_241.pdf Professor Ye’s Google Scholar page: https://scholar.google.com/citations?user=VSP72CMAAAAJ&hl=en
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/34772830
info_outline
For-Profit Drivers of Poor Health in America 2: Pharmaceutical Industry
01/02/2025
For-Profit Drivers of Poor Health in America 2: Pharmaceutical Industry
Among high income countries the United States spends the most on health care and yet has the lowest life expectancy. A high percentage of Americans suffer with chronic diseases including obesity, diabetes, cardiovascular disease, mental disorders, and Alzheimer’s or Parkinson’s diseases. There are several reasons why people living in the wealthiest country have poor health all attributable to unrestrained capitalism. In this episode I talk about issues with pharmaceutical industry that contribute to the overall poor quality of health and health care in America with a focus on drugs for neurological disorders. Drug prices in the US are much higher than in other countries and prices are increasing at a rate more than 5 times the rate of inflation. Pharmaceutical companies spend nearly twice as much on marketing as on research and development and overstate their costs for drug development by ~400 percent. The US is one of only two countries that permit direct advertising of drugs to consumers. Pharmaceutical company representatives lobby doctors and congress. There are also major issues concerning clinical trials of drugs including conflicts of interest, lack of data transparency, and lack of head-to-head comparisons of a new drug with an existing drug. There are potential solutions to these problems but will require major new government regulations. https://pubmed.ncbi.nlm.nih.gov/31034803/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8649053/pdf/nihms-1751070.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/34701095
info_outline
Jason Shepherd: The Arc Protein – From Viral Origins to Center Stage in Neuroplasticity and Disease
12/20/2024
Jason Shepherd: The Arc Protein – From Viral Origins to Center Stage in Neuroplasticity and Disease
In this episode I talk with Professor Jason Shepherd about his discoveries concerning a fascinating protein called Arc. In response to synaptic activity Arc levels rapidly increase in postsynaptic dendrites as a result of local translation of the Arc mRNA in the dendrites. Arc plays a critical role in long-term memory although it is not necessary for learning. But perhaps the most interesting twist in the Arc story comes from the Shepherd labs discovery that Arc can self-assemble into highly ordered structures that are essentially identical to the capsids that form the coat of viruses. I talk with Jason about evidence that Arc can bind mRNAs and transfer them from one neuron to another in extracellular vesicles. These findings reveal a whole new mechanism for regulating neuronal network function. Moreover, recently Jason and his lab members have demonstrated a key role for Arc in the trans-neuronal propagation of Tau pathology which is an important advance in understanding how the neurodegenerative process spreads throughout neuronal networks in Alzheimer’s disease and other neurodegenerative disorders – and also has implications for novel approaches for halting the disease process. LINKS: The Shepherd laboratory page: https://www.shepherdlab.org/ Key publications from the Shepherd lab: https://pmc.ncbi.nlm.nih.gov/articles/PMC8041237/pdf/nihms-1661230.pdf https://www.cell.com/action/showPdf?pii=S0092-8674%2817%2931504-0 https://pmc.ncbi.nlm.nih.gov/articles/PMC11526995/pdf/nihpp-2024.10.22.619703v1.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/34549585
info_outline
For-Profit Drivers of Poor [Brain] Health in America 1: Food Industries
12/11/2024
For-Profit Drivers of Poor [Brain] Health in America 1: Food Industries
Among high income countries the United States spends the most on health care and yet has the lowest life expectancy. A high percentage of Americans suffer with chronic diseases including obesity, diabetes, cardiovascular disease, mental disorders, and Alzheimer’s or Parkinson’s diseases. There are several reasons why people living in the wealthiest country have poor health all attributable to unrestrained capitalism. In this episode I talk about how large-scale monoculture crops used to produce addictive ultraprocessed sugars such as high fructose corn syrup adversely affect health including brain health. The widespread availability of such obesogenic high-calorie ultraprocessed foods at low prices have propelled a transgenerational epidemic of obesity, diabetes and associated chronic brain disorders. Increasingly sedentary lifestyles exacerbate the problem. In also talk about the health benefits of a range of organically grown vegetables and fruits with a focus on a few specific chemicals they produce that act on cells in ways that bolster their function and resilience. Here are links to a few articles that provide more detail on the problem and potential solutions. https://pmc.ncbi.nlm.nih.gov/articles/PMC9904196/pdf/nihms-1868184.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC8748512/pdf/41467_2021_Article_27645.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC6779523/pdf/nihms-1537205.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC5841445/pdf/nihms946635.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC4081729/pdf/pr.113.007757.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC4586293/pdf/nihms678801.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/34394120
info_outline
Bruno Rossion: Elucidating the Remarkable Ability of the Human Brain to Recognize Faces
12/03/2024
Bruno Rossion: Elucidating the Remarkable Ability of the Human Brain to Recognize Faces
Humans have the amazing ability to instantly recognize the faces of hundreds or even thousands of people they have previously met or seen in pictures or movies. Studies of people with brain injuries that render them incapable of recognizing faces and recordings of neuronal activity in people during face recognition have shown that networks in the occipital and temporal lobes adjacent to the visual cortex mediate facial recognition. Professor Bruno Rossion is at the forefront of research that is revealing the neurophysiological underpinnings of face recognition. By recording and stimulating neurons in the face recognition circuits of numerous research participants Rossion’s laboratory has elucidated how the brain captures and recalls the gestalt of a face without dwelling on specific features of the face. LINKS: Review articles on the neurobiology of face recognition: https://pmc.ncbi.nlm.nih.gov/articles/PMC9954066/pdf/brainsci-13-00354.pdf https://www.sciencedirect.com/science/article/pii/S0028393224000800?via%3Dihub https://www.sciencedirect.com/science/article/pii/S0149763424000034?via%3Dihub
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/34262325
info_outline
Bioenergetics and Brain Health 4: Brain Aging, Alzheimer’s and Parkinson’s Diseases, and Stroke
11/26/2024
Bioenergetics and Brain Health 4: Brain Aging, Alzheimer’s and Parkinson’s Diseases, and Stroke
In this final episode of the Bioenergetics and Brain Health series I talk about changes that occur in brain cells during normal aging, and in Alzheimer’s disease, Parkinson’s disease, and stroke with emphasis on alterations upstream and downstream of cellular energy metabolism. The episode concludes with examples of therapeutic interventions that target those age- and disease-related alterations. LINKS: Hallmarks of Brain Aging https://pmc.ncbi.nlm.nih.gov/articles/PMC6039826/pdf/nihms979409.pdf Brain Energy Rescue: https://pmc.ncbi.nlm.nih.gov/articles/PMC7948516/pdf/nihms-1624328.pdf The Hormesis Principle of Brain Health and Resilience https://pmc.ncbi.nlm.nih.gov/articles/PMC5209274/pdf/nihms834422.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/34154775
info_outline
Bioenergetics and Brain Health 3: How Exercise and Fasting Enhance Neuroplasticity and Resilience
11/19/2024
Bioenergetics and Brain Health 3: How Exercise and Fasting Enhance Neuroplasticity and Resilience
In this third podcast in the Bioenergetics and Brain Health series I talk about how intermittent exercise and fasting affect brain function, neuroplasticity, and resilience. Research has shown that both of these bioenergetic challenges can enhance learning and memory, improve mood, counteract aging, and protect neurons against injury and disease. I provide an overview of evidence that over periods of weeks and months cycling between challenge (exercise and fasting) and recovery (resting, eating, sleeping) periods stimulates the formation of new synaptic connections between neurons, increases neurogenesis, and bolsters neuronal stress resistance. These adaptations of brain cells to bioenergetic challenges are mediated by hormonal factors released from peripheral organs including ketones, and by changes in gene expression in brain cells. A better understanding of how bioenergetic challenges affect the brain provides a rationale for incorporating exercise and fasting into lifestyles and is also revealing new approaches for pharmacological interventions in neurological disorders.
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/33993767
info_outline
Bioenergetics and Brain Health 2: Mitochondrial Dynamics, Biogenesis, Disposal, and Signaling
11/11/2024
Bioenergetics and Brain Health 2: Mitochondrial Dynamics, Biogenesis, Disposal, and Signaling
This is the second in a series of presentations on the interrelationships between energy metabolism, brain function and resilience, and disease processes. In this episode I describe how mitochondria are moved about within axons and dendrites, how mitochondria divide, fuse with each other, and are eliminated when they become dysfunctional. Importantly, mitochondria influence and respond to activity in neuronal networks in ways that optimize energy efficiency and promote the formation and maintenance of synapses between neurons. I also introduce the next presentation which will focus on how physical exercise and intermittent fasting affect brain function, plasticity, and resilience.
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/33879377
info_outline
Josh Dubnau: Endogenous Retroviruses and Retrotransposons in Brain Aging and Degenerative Disorders
11/05/2024
Josh Dubnau: Endogenous Retroviruses and Retrotransposons in Brain Aging and Degenerative Disorders
More than 40 percent of the human genome consists of retrotransposons which are DNA sequences related to retroviruses that can jump within the genome and have the ability to replicate although most are dormant. In this episode Professor Josh Dubnau at the University of Stony Brook talks about endogenous retroviruses and retrotransposons and recent evidence that some of them are activated in neurons during brain aging and may play roles in the pathogenesis of ALS, frontotemporal dementia, and Alzheimer’s disease. Using the powerful molecular genetic tools in Drosophila models the Dubnau and his team have shown that activated retrotransposons can cause pathological aggregation of the protein TDP43 in neurons and the spreading of the TDP43 pathology between cells similar to that which occurs in ALS and frontotemporal dementia. This basic research advances an understanding of brain aging and neurodegenerative disorders and suggests new approaches for preventing and treating these disorders. LINKS Dr. Dubnau’s web page https://renaissance.stonybrookmedicine.edu/anesthesiology/research/Dubnau Review article on endogenous retroviruses and retrotransposons and their putative roles in neurodegenerative disorders https://pubmed.ncbi.nlm.nih.gov/38663088/ Original research articles https://pmc.ncbi.nlm.nih.gov/articles/PMC9944888/pdf/41467_2023_Article_36649.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC8096092/pdf/pgen.1009535.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC6783360/pdf/nihms-1536529.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/33792437
info_outline
Bioenergetics and Brain Health 1: Evolutionary Perspective and Overview of Brain Energy Metabolism
10/29/2024
Bioenergetics and Brain Health 1: Evolutionary Perspective and Overview of Brain Energy Metabolism
This is the fist in a short series of presentations on the interrelationships between energy metabolism, brain function and resilience, and disease processes. Overindulgent sedentary lifestyles are increasingly common with adverse consequences for trajectories of brain health in current and future generations. In this series I review findings from studies of humans and animals that are elucidating the cellular and molecular mechanisms by which energy intake and exercise affect structural and functional neuroplasticity. This topic is considered from a bioenergetic perspective with emphases on brain evolution, developmental neurobiology, adult neuroplasticity and disorders of mood and cognition.
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/33668362
info_outline
Ziv Williams: Encoding Social Cognition and Language in Individual Neurons and Neuronal Ensembles
10/22/2024
Ziv Williams: Encoding Social Cognition and Language in Individual Neurons and Neuronal Ensembles
Every day we communicate with and influence others via language, decision-making, and actions. The complexities of human social interactions and language begs the question of how the brain processes the relevant incoming information and then generates responses so rapidly and effortlessly. Neurosurgeon Ziv Williams and his team at Harvard Medical School have made major advances in answering these questions. By recording the activities of hundreds of individual neurons in the brains of non-human primates in game-theory paradigms of social cooperation and conflict he has identified neurons in the prefrontal cortex that encode social agent identity. Moreover, by recording from neurons in the brains of human patients undergoing brain surgery his team has identified neurons involved in single elements of speech production or in the semantic encoding during language comprehension. These findings not only advance an understanding of the neurobiological underpinnings of social interactions and language, but also provide insight into disorders involving alterations in these processes. LINKS Dr. Williams Harvard webpage https://zivwilliams.mgh.harvard.edu/ Neuronal circuits for social decision-making https://pmc.ncbi.nlm.nih.gov/articles/PMC8517320/pdf/fnins-15-720294.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC8571805/pdf/nihms-1752328.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC7990696/pdf/nihms-1654341.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC10866697/pdf/41586_2023_Article_6982.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC11254762/pdf/41586_2024_Article_7643.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/33568132
info_outline
Antoinette M van den Brink and Rolf Fronczek: Causes and Therapy for Migraine and Cluster Headaches
10/15/2024
Antoinette M van den Brink and Rolf Fronczek: Causes and Therapy for Migraine and Cluster Headaches
One in seven people experience migraine headaches while others suffer with even more debilitating cluster headaches. The causes of these headaches are not fully understood and current treatments provide only partial relief. In this episode pharmacologist Antoinette van den Brink and neurologist Rolf Fronczek describe the clinical features of these headaches, the current understanding of their causes, and hormonal and environmental factors that can trigger the headaches. Drugs that inhibit the peptide CGRP and electrical stimulation of the occipital nerve are among treatments shown to be effective in reducing headache intensity or duration. LINKS University webpages: https://www.erasmusmc.nl/en/research/researchers/maassen-van-den-brink-antoinette https://hoofdpijnonderzoek.nl/en/team/dr-rolf-fronczek/ Migraine headache articles https://journals.sagepub.com/doi/epub/10.1177/03331024241238153 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863119/pdf/10194_2024_Article_1724.pdf Cluster headache articles https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018790/pdf/40263_2019_Article_696.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10755111/pdf/main.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/33465322
info_outline
Andrea Luppi: Consciousness and Brain Function Through the Lens of Time, Space, and Information
10/08/2024
Andrea Luppi: Consciousness and Brain Function Through the Lens of Time, Space, and Information
Consciousness is one’s awareness of electrochemically conveyed information coming into the brain from the environment via sensory pathways or generated within the brain’s neuronal networks (i.e., thoughts). In popular culture ‘consciousness’ is often portrayed as a mysterious concept or process. However, research that examines the effects of anesthetics, sleep, brain injuries, and psychedelics on neuronal network activity using fMRI, EEG and other technologies is revealing the circuits and activity patterns that enable consciousness. In this episode University of Cambridge Professor Andrea Luppi talks about his research on the neurochemical and neural network level underpinnings of consciousness. His integration of fMRI and brain connectome data suggest the importance of ‘gateway neuronal networks’ and ‘broadcasters’ (executive control networks) in human consciousness. We also discuss consciousness from philosophical and evolutionary perspectives. LINKS Professor Luppi’s profile at the University of Cambridge https://neuroscience.cam.ac.uk/member/al857/ Recent review article on consciousness https://www.cell.com/action/showPdf?pii=S0166-2236%2824%2900087-0 Gateway regions and broadcasters https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257694/pdf/elife-88173.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/33375042
info_outline
Richard Lu: OPCs and Oligodendrocytes – Roles in Brain Development, Function, and Cancer
10/01/2024
Richard Lu: OPCs and Oligodendrocytes – Roles in Brain Development, Function, and Cancer
In this episode Richard Lu – a professor of pediatrics at the University of Cincinnati Chldren’s Hospital talks about a type of stem cell in the brain called oligodendrocyte progenitor cells (OPC). OPC normally differentiate into the oligodendrocytes that wrap around the axons of neurons providing insulation that greatly speeds up the propagation of electrical impulses. These cells also provide nutrients to neurons and produce proteins that promote the survival of the neurons. But OPC can and unfortunately do become transformed into cancer cells. Dr. Lu talks about the normal roles of OPC in brain development and how they can form brain tumors. LINKS: Dr. Lu’s laboratory web page: https://www.cincinnatichildrens.org/research/divisions/e/ex-hem/labs/lu Oligodendrocytes – review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018611/pdf/nihms-1686441.pdf Oligodendrocytes – Brain repair and cancers https://www.sciencedirect.com/science/article/pii/S0969996120303156?via%3Dihub
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/33279912
info_outline
Visar Berisha and Julie Liss: Automated Speech Analysis to Evaluate Brain Function and Disease
09/24/2024
Visar Berisha and Julie Liss: Automated Speech Analysis to Evaluate Brain Function and Disease
Arizona State University Professors Visar Berisha and Julie Liss have combined their expertise in engineering and speech communication to develop and apply novel automated speech analysis technology to the field of neurological disorders. Because of the complexity of human speech and the brain circuits involved speech analysis can provide a window into multiple domains of brain function. In this episode they talk about their research and how speech analysis can be used as a tool for cross sectional and longitudinal studies of people with or a risk for brain dysfunction. Their published findings range from studies of NFL football players to patients with ALS or a mental disorder. Automated speech analysis may prove useful in the early diagnosis of neurodegenerative disorders and for evaluation of the efficacy of treatments. LINKS Review article on automated speech analysis and its applications https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074691/pdf/nihms-1062578.pdf Study of NFL players https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939664/pdf/nihms-861058.pdf Early diagnosis of ALS https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555482/pdf/41746_2020_Article_335.pdf Assessment of mental health https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031731/pdf/sbac176.pdf Potential for early diagnosis of Alzheimer’s disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922000/pdf/nihms-1062581.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/33184587
info_outline
Erika Augustine: Challenges of Rare Childhood Neurological Disorders Exemplified by Batten Diseases
09/19/2024
Erika Augustine: Challenges of Rare Childhood Neurological Disorders Exemplified by Batten Diseases
There are approximately 7000 rare diseases each affecting fewer than 200,000 Americans. Most rare disorders are caused by gene mutations, manifest in childhood, include neurological problems, and progress rapidly resulting in death in the first several decades of life. Examples include fragile X and Rett syndromes, some childhood epilepsies, Batten diseases, and several types of ataxias, In most instances there are no treatments that slow or reverse the disease process. In this episode I talk with Professor Erika Augustine who is the Associate Chief Science Officer and Director of the Clinical Trials Unit at the Kennedy – Krieger Institute which is devoted to research on and treatment of neurological conditions caused by genetic disorders, birth complications, or traumatic injuries with a focus on children and adolescents. Dr. Augustine talks about the scope of the problems faced by patients with a rare disorder, their families, neurologists, government agencies, and the pharmaceutical industry. To exemplify both the challenges and progress towards effective treatments Dr. Augustine focuses on Batten diseases caused by mutations that impair lysosome functions and cause severe progressive neurological deficits that begin early in life. An effective treatment for one of the Batten diseases was recently approved by the FDA providing one of the first successes in moving from basic research to the clinic. LINKS: Dr. Augustine’s biography in Wikipedia: https://en.wikipedia.org/wiki/Erika_F._Augustine Kennedy – Krieger Institute: https://www.kennedykrieger.org/?gad_source=1&gclid=CjwKCAjwl6-3BhBWEiwApN6_ksQGX9fZCTAZpUSzJNw4sHdr2EyRmm_d3tYPHzQpAEOpBuC0uDGZVRoCSGQQAvD_BwE Batten Diseases Clinical Trials: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736171/pdf/nihms-1641434.pdf Enzyme replacement therapy for CLN2 Batten disease: https://www.pedneur.com/action/showPdf?pii=S0887-8994%2820%2930149-1 Gene therapy for rare neurological disorders: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527017/pdf/fnmol-14-695937.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/33122167
info_outline
Understanding and Counteracting Brain Aging
09/12/2024
Understanding and Counteracting Brain Aging
In this episode I provide an overview of what happens in brain cells during aging and how those changes result in impaired brain function and predispose to Alzheimer’s and Parkinson’s diseases. I then describe three lifestyle anti-aging interventions that are known to slow brain aging and counteract disease process: physical exercise; intermittent fasting; and intellectual challenges. LINKS Hallmarks of brain aging: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039826/pdf/nihms979409.pdf Exercise and brain health: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880155/pdf/cshperspectmed-BEX-a029736.pdf Intermittent fasting and brain health: https://www.amazon.com/Intermittent-Fasting-Revolution-Optimizing-Performance/dp/0262046407 Environmental enrichment: https://pubmed.ncbi.nlm.nih.gov/30723309/ Hormesis and brain health: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096685/pdf/10.1177_1559325818784501.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/33026362
info_outline
Shiqian Shen: Gut – Immune – Brain Communications in Chronic Pain Reveal New Avenues for Treatments
08/30/2024
Shiqian Shen: Gut – Immune – Brain Communications in Chronic Pain Reveal New Avenues for Treatments
Chronic pain is a highly prevalent problem in need to improved treatments. In this episode I talk with Dr. Shiqian Shen of Harvard Medical School about his research on interactions between the immune and nervous systems in chronic pain. He has found an interesting connection between the gut microbiota, immune cells, and neurons in chronic pain. These findings suggest new approaches for treating chronic pain. LINKS https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575957/pdf/nihms887104.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9974100/pdf/jci-133-166408.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320346/pdf/ACEL-23-e14177.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/32809552
info_outline
Daniel Pine: Understanding and Treating Anxiety Disorders in Children and Adolescents
08/21/2024
Daniel Pine: Understanding and Treating Anxiety Disorders in Children and Adolescents
Anxiety disorders are all too common in children and adolescents and their incidence has increased considerably during the past decade. Social interactions (positive or negative) in the home, schools, and the digital world have a major influence on a child’s risk for anxiety and major depression. In this episode I talk with Dr. Danny Pine at the National Institute of Mental Health who has devoted his career to the problem of mental health problems in children. His research has advanced an understanding of the complex factors that determine whether or not a child develops an anxiety disorder, the brain circuits involved, and the behavioral and pharmacological interventions that can provide effective treatments. LINKS Dr. Pine’s NIH webpage: https://www.nimh.nih.gov/research/research-conducted-at-nimh/research-areas/clinics-and-labs/edb/sdan Articles https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248771/pdf/nihms-1797515.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490291/pdf/nihms-1734583.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931491/pdf/nihms-1858084.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/32671952
info_outline
Ronald DePinho: Aging and Cancer Research Elucidates Neurodegenerative Mechanisms and Treatments
08/14/2024
Ronald DePinho: Aging and Cancer Research Elucidates Neurodegenerative Mechanisms and Treatments
Cells in all organ systems experience the same ‘hallmarks of aging’ which include the accumulation of oxidatively damaged proteins, DNA, membranes and mitochondria, impaired DNA repair and autophagy, senescence, and inflammation. In this episode Professor Ron DePinho of the MD Anderson Cancer Center in Houston talks about his remarkable career during which he and his trainees established fundamental mechanisms that control cell proliferation and differentiation in normal development and how alterations in these mechanisms result in aging and cancers. He then describes how the telomerase protein influences hallmarks of aging by controlling gene expression, and how age-related reductions in telomerase levels contribute to normal aging and the pathogenesis of Alzheimer’s disease. Ron and his colleagues have recently identified a chemical called TAC that can increase telomerase levels in cells. Treatment of old mice with TAC rejuvenates multiple organ systems, and can restore neuroplasticity and cognition in mouse models of Alzheimer’s disease. LINKS: DePinho laboratory web page: https://www.mdanderson.org/research/departments-labs-institutes/labs/depinho-laboratory.html Related Articles: https://www.cell.com/action/showPdf?pii=S0092-8674%2820%2931750-5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733214/pdf/nihms487161.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759755/pdf/nihms-1761822.pdf https://pubmed.ncbi.nlm.nih.gov/38908367/
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/32574507
info_outline
Dimitrios Kapogiannis: Messages in Neural Nanobubbles: Extracellular Vesicles and Brain Disorders
08/07/2024
Dimitrios Kapogiannis: Messages in Neural Nanobubbles: Extracellular Vesicles and Brain Disorders
All cells including neurons in the brain release tiny (~ 100 nanometers in diameter) bubble-like vesicles that contain various molecules produced by the cell. These extracellular vesicles (EVs) are thought to have a variety of functions including sending molecular messages between cells and removing molecular garbage from the cells. Some EVs released from cells throughout the body and brain make their way into the bloodstream. Dimitrios Kapogiannis at the National Institute on Aging Biomedical Research Center in Baltimore, developed a technology for isolating EVs produced by neurons from the blood. By measuring amounts of abnormal Tau protein in neuronal EVs from patients with Alzheimer’s disease (AD) and controls, and in longitudinal studies of people in the years preceding their cognitive impairment, he showed that his test can identify people who will very likely become symptomatic. It turns out that neuronal EVs have insulin receptors in their membrane and Dimitrios provided evidence that neuronal EVs from AD patients exhibit insulin resistance. Because intermittent fasting can increase the sensitivity of cells to insulin and is effective in countering the disease process in AD mouse models, Dimitrios performed a clinical trials of intermittent fasting in older individuals with insulin resistance and found that it improved their performance on several memory tests. More recently he headed a clinical trial of a ketone ester in patients in older people at risk for AD. This episode is all about EVs – where they come from, the kinds of molecules they contain, their normal functions, and changes in EVs in Alzheimer’s disease (AD) and other brain disorders that can be used for diagnosis and in clinical trials. LINKS Dr. Kapogiannis’ NIA webpage: https://www.nia.nih.gov/about/staff/kapogiannis-dimitrios Review articles on EVs: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439289/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985115/pdf/nihms-1878107.pdf Key publications: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314222/?report=printable https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6632160/?report=printable https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146429/pdf/cells-10-00993.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060702/pdf/awac258.pdf
/episode/index/show/0584c51e-6018-4b82-b9ff-c9150f2584f2/id/32476712