The usual approach for developing treatments for brain disorders is to make a drug that acts on a specific molecular target. But this approach has largely failed. In this episode I talk with Professor Raj Ratan at Weill Cornell Medicine about ways to tap the intrinsic ability of brain cells to respond adaptively to challenges – metabolic, oxidative, and biosynthetic – in ways that protect them against pathological processes such as those occurring in stroke, traumatic brain injury, Alzheimer’s and Parkinson’s diseases. Raj and his colleagues have developed several different interventions that are highly effective in animal models of stroke and Alzheimer’s disease. Intermittent dosing with such treatments can activate evolutionarily conserved complex and integrated gene expression responses in brain cells that bolster stress resistance and enable recovery and repair.

LINKS

Dr. Ratan’s laboratory webpage: https://burke.weill.cornell.edu/ratan-lab/people/rajiv-r-ratan-md-phd

Selenium protects against ferroptosis and stroke:

https://www.cell.com/action/showPdf?pii=S0092-8674%2819%2930327-7

HIF prolyl hydroxylase inhibition for stroke ?:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390817/pdf/jcbfm201228a.pdf

2-deoxyglucose for experimental stroke and Alzheimer’s disease:

https://pdf.sciencedirectassets.com/272195/1-s2.0-S0896627322X00196/1-s2.0-S0896627323004725/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEDMaCXVzLWVhc3QtMSJHMEUCIC02vyvj45WOEJ6cJ%2BO3zLTkbyrmywu3UV2k0tE99ISSAiEAm%2B2Ga7NWSJSMResvqmDJZn87epQuNnoQNFUS%2FM1xh1QquwUIvP%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FARAFGgwwNTkwMDM1NDY4NjUiDKWhJaRjapFKYPcUuSqPBXZt7z6Y%2F%2FFQDTJZNd63uYfGqFnqQ5FraRDyTiOoShRDuHZ%2FFurOQBeXcKh34xKHbYXG3aw4aZ1qknn5rmr5oZKXJEnQKSDQbTIMaZfam7JN223W98JHQjFExQSg1IpIXsJIOpPDRC6SnxewO9HWfK5VsT22Yd1%2FvfyJ6TNHysLd5avZUcCzNwd1Tzg%2F7n5boUZ3bv8ksKJTbXKIa6URMIpJ1Elry%2Bx2cOHHsudyKQHl38MnqJfyBDlsvlSdlvPvqZyiDl41UPQ4wQXG8zxZKtwc4W9Nz3bBDtosARXGGykFw5PGjP8vljwzBmpAIPA2vntVuzKB1GVCjSOPeZIfB%2FT7gbpjO6XFPulqMJfoZSHMIP6U5%2Baluyz25U7gQI0DlHQuqHHQlPp16W1%2FZUDpV6qfCWLDFa86hE3Mk2bUdhVxC7%2F1avNNvRjCVubyOhIY9MrjdQSpJx5FCd9yj2KkOAQSxn0T8ZQ2HZl10eOzNJBv0flA%2BQXys58UySTYb0QHKIOrD1YbjW0M%2B1qrdzwunAYlpugxnqm64BMuZL1aUWPQUzD6Xu59k23wj9IKZ7ysz8OJgHiaxCL%2BmrhMtF1wBO5rkKomJdordmx%2B46wjknrwW9sUy4NFS74JkUYhIGjiZ1lQ6E%2BFcjJe1R%2FeLOfxx2VfcbXyzyjaVgNaS16fRYydqoT0r1xth2rMdDADuFYvT1Mxw909AAZ6ja4ur%2Bcb56eAT7kbwtKDDsTq3l%2FlTVEwX8zAkagg%2Ba2yg2RUF26zTiA9ur%2FR1keAROBxVFyOyhBFg0tX2aHFaPkRmbTLOOeslpmFdWYlYhhLn%2FDgHzXafbqJ6MS29hnDJVpSZNwtkILsv6Fvf7MlT%2FU%2Fdet6sI4w6oKBswY6sQGQdr%2Fyh54qyfoNjp7vTeWRp56lw26rZzdq5JzhPL7AooWioriINJoD5PBTfQ6P9kkjgrbt3KgE0gLwdquV5t8cPemG6Ud6J7FFfiCqdduYGnkdgvqay00lKumUQWivFmbLK1KwV3ZTiHqK6k%2BnwmjmJx6TC2wOb0ri18vlPuaf9tL3twxztVgBXpqCEHtrk2xoln3A%2FxRta1ENiKDj3i%2BeEJsq8LA5%2Ft1DnHnQTTngNeI%3D&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20240605T120054Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTYTBFTALVN%2F20240605%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=a28ce7980230f4e238a2b9b01639b4a3771986228a5b71afee77812caae7ec5a&hash=2c8062367af976e82b072e2c70fee70c72e3b4c101e00ffb8e600353969e084d&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S0896627323004725&tid=spdf-39789cb0-1edf-4028-964c-0b8b685189bb&sid=957e62f0674d764d5259d1032c07123fda92gxrqa&type=client&tsoh=d3d3LXNjaWVuY2VkaXJlY3QtY29tLnByb3h5MS5saWJyYXJ5LmpodS5lZHU%3D&ua=0f105b59005f5e555053&rr=88f00141e8697283&cc=us

Anxiety, attention-deficit disorder, depression and loneliness have increased dramatically recently as a result, at least in part, of information overload and a relative lack of time for ‘slow thinking’ and self-reflection. In this episode I talk with University of Wisconsin Professor Richard (Richie) Davidson about his research on mindfulness meditation and the neuroscience of happiness. His research has shown that mental well being is a skill that can be learned. He describes the effects of meditation on neuronal networks and well being and talks about ‘the four pillars of a healthy mind: attentiveness, communication, insight, and purpose. He and his colleagues have developed a free App called ‘The Healthy Minds Program’ which has been demonstrated to be effective in bolstering these four pillars.

LINKS

Center for Healthy Minds: https://centerhealthyminds.org

Free Healthy Minds Program App: https://hminnovations.org/meditation-app?gad_source=1

Review articles on mindfulness-based intervention research:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609495/pdf/nihms-1521077.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597263/pdf/nihms-1025535.pdf

Review article on challenges in research on mindfulness and meditation:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627495/pdf/nihms704718.pdf

Many of the drugs that are used recreationally or prescribed by physicians were originally isolated from plants. Increasing evidence suggest that in many instances the function of such phytochemicals is to communicate with insects and other organisms in ways that enhance the fitness of the plants. Pamela Maher at the Salk Institute has been working to identify phytochemicals that can protect neurons from being damaged in experimental models of neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s disease.. Here she talks about several phytochemicals that are particularly promising including fisetin, sterubin, cannabinol, and a synthetic derivative of fisetin called CMS121.

LINKS:

Fisetin: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990461/pdf/bpl-6-bpl200104.pdf

Sterubin: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309122/pdf/main.pdf

CMS121: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394765/pdf/main.pdf

Cannabinol: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11002867/pdf/main.pdf

Perspective article on neuroprotective phytochemicals: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841445/pdf/nihms946635.pdf

In this episode I talk with Professor Sandrine Thuret at Kings College London about her research on how different molecules in the diet affect neuroplasticity in general and hippocampal neurogenesis in particular. She has shown in preclinical studies that certain dietary factor including omega-3 fatty acids can counteract the adverse effects of chronic psychological stress on neurogenesis. She has also shown that intermittent fasting enhances hippocampal neurogenesis and improves cognition. Thuret has also found that factors circulating in the blood can either enhance or inhibit neurogenesis, and may either promote brain health or contribute to brain dysfunction in disorders such as depression and Alzheimer’s disease.

LINKS:

Effects of intermittent fasting on neurogenesis and memory:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760057/pdf/41380_2021_Article_1102.pdf

Omega-3 fatty acids and neurogenesis:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341841/pdf/41398_2020_Article_908.pdf

Phytochemicals and brain resilience:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081729/pdf/pr.113.007757.pdf

Serum factors:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10151193/pdf/awac472.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612606/pdf/ad-12-8-2151.pdf

Bacteria in the gut play essential roles in the metabolism of dietary nutrients. But a recent explosion of research has revealed influences of microbes in the gut on brain function in health and in anxiety disorders, depression, and possibly Alzheimer’s and Parkinson’s diseases. Professor John Cryan at University College in Cork Ireland is at the forefront of this research. In this episode I talk with John about how diet and lifestyle affect the gut microbiome and the mechanisms by which these microbes can affect brain health. Those mechanisms include roles for the vagus nerve and chemicals produced by gut bacteria that travel through the blood and into the brain. We also discuss translational research aimed at optimizing the gut bacterial composition in ways that promote lifelong brain health or for the treatment of neurological disorders.

LINKS:

Professor Cryan’s webpage: https://www.ucc.ie/en/apc/people/johncryan/

Book ‘The Psychobiotic Revolution’: https://www.amazon.com/Psychobiotic-Revolution-Science-Gut-Brain-Connection/dp/142621846X

Review articles:

https://www.sciencedirect.com/science/article/pii/S0959438822001465?via%3Dihub

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321864/pdf/nmaa181.pdf

https://www.cell.com/action/showPdf?pii=S1550-4131%2820%2930067-X

David Nutt has made major contributions to understanding mechanisms by which psychoactive drugs affect the brain and has conducted numerous clinical trials of a wide range of drugs in patients with various mental disorders. He has also been an outspoken critic of the disconnect between drug science and government drug policies. For example, alcohol is legal, widely available, and causes tremendous harm to individuals and society. On the other hand psychedelics are illegal and yet very safe and can be very beneficial for mental health. In this episode I talk with Professor Nutt about the relative harms and benefits of different drugs to individuals and society. His efforts and those of many other scientists and psychiatrists are pushing governments to accept the facts and help facilitate rather than obstruct science-based progress in drug research and use of that knowledge for medicine and society.

David Nutt is a distinguished professor in the Division of Brain Sciences at Imperial College in London. He is the founder and chairman of Drug Science and host of the Drug Science Podcast.

LINKS:

Drug Science website: https://www.drugscience.org.uk/drug-information/?gad_source=1&gclid=CjwKCAjwuJ2xBhA3EiwAMVjkVG_peCbmMCI9tKIYTUldYjmfjHNxCLeLX2WYvkLPezA7zaJpciU8HhoCGHcQAvD_BwE

Drug Science podcast: https://open.spotify.com/show/2hLSRIS777SKphWxv4HyDK

Recent relevant articles:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291338/pdf/fpsyt-14-1183740.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669276/pdf/fpsyt-13-1027159.pdf

https://www.sciencedirect.com/science/article/pii/S0028390822003161?via%3Dihub

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625009/pdf/nutrients-13-03938.pdf

Some elderly individuals remain cognitively ‘sharp as a tack’ despite the accumulation of large amounts of amyloid in their brains, whereas others exhibit profound cognitive impairment with less amyloid pathology. In this episode Columbia University Professor Yaakov Stern talks about the concepts of ‘cognitive reserve’ and ‘brain maintenance’ and how he and others have elucidated factors that explain individual differences in cognitive trajectories during aging. The data show that regular exercise and intellectually challenging endeavors promote successful brain aging in the absence or presence of Alzheimer’s disease pathology. We also discuss neural mechanisms that may explain cognitive reserve and brain maintenance during aging.

LINKS:

Professor Stern’s webpage at Columbia University:

https://www.neurology.columbia.edu/profile/yaakov-stern-phd

Review articles on cognitive reserve and brain maintenance:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507991/pdf/nihms416640.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517622/pdf/acab049.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859943/pdf/nihms-1530897.pdf

What are the foundational principles by which acquired information is organized and processed in the human brain? In this episode University of Rome Professor Anna Borghi talks about several prominent working theories of cognition including embodied cognition (interactions with objects and other people), inner speech, and abstract concepts. She talks about how language is a prominent feature of these theories and the methods used to test these theories. We also touch on evolutionary and developmental perspectives that help explain these cognitive abilities.

LINKS

The embodied mind extended: using words as social tools:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640182/pdf/fpsyg-04-00214.pdf

Inner speech: https://www.cell.com/action/showPdf?pii=S1364-6613%2823%2900210-3

Abstract concepts: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674746/pdf/426_2022_Article_1698.pdf