Measles, Polio, COVID, AIDS, tick-borne encephalitis, Lyme disease, meningitis, yellow fever, and Ebola are examples of diseases that can be fatal and those who survive the infection may have long-term neurological disability resulting from damage to neural circuits caused by the virus or bacteria. Effective vaccines have been developed for all of these infectious diseases except AIDS for which vaccines against HIV are being developed. In this episode I talk with Dr. Kiran Thakur, Director of the Neuroinfectious Disease Program at Columbia University, about the impact of these infectious agents on the brain, the threat of their resurgence, and the importance of world-wide surveillance and vaccination programs to prevent mortality and long-term disability, and to prevent the emergence and spread of new strains of viruses and bacteria. We also discuss treatments for patients whose brains have been infected. Unfortunately, currently available treatments are in many instances not effective in reducing morbidity and mortality, a fact that bolsters the importance of vaccination.

LINKS

Thakur laboratory page:

https://www.neurology.columbia.edu/research/research-labs/thakur-lab

Review article on the global threat of vaccine-preventable neurological diseases:

https://www.nature.com/articles/s41582-025-01172-w

Review article on long COVID:

https://www.nature.com/articles/s41572-025-00674-7

Advances in treatments for neuroinfectious diseases:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11418331/pdf/10.1177_20499361241274246.pdf

Climate change, habitat degradation, and the emergence of new neuroinfectious agents:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11412215/pdf/10.1177_20499361241274206.pdf

Protein nitrosylation a process by which redox reactions of nitric oxide (NO) and proteins result in covalent modification of the sulfur in the amino acid cysteine resulting in S-nitrosothiol (SNO). In this episode I talk with Scripps Research Professor Stuart Lipton about his research career highlighting the discovery that protein nitrosylation occurs on numerous proteins in neurons and contributes to the dysfunction and degeneration of neurons in Alzheimer's disease and other neurodegenerative disorders. Prior to his discovery of protein nitrosylation, Stuart worked to better understand the process of excitotoxicity which is involved in the demise of neurons in many neurological disorders. This work led to the development of the only drug – memantine – that slows the progression of Alzheimer's disease, albeit only somewhat. Recently, Stuart was awarded a grant to elucidate the effects of air pollution on the brain with a focus on the role of chemical reactions resulting in protein nitrosylation. Stuart and his team are now working to develop drugs that specifically prevent the chemical reactions that result in excessive protein nitrosylation as treatments for neurodegenerative disorders.

LINKS

Lipton's page at the Scripps:

https://www.scripps.edu/faculty/lipton/

Review articles

https://pmc.ncbi.nlm.nih.gov/articles/PMC11624102/pdf/nihms-2029640.pdf

https://www.nature.com/articles/nrd1958

Original research articles:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11892585/pdf/pnas.202418179.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC2823371/pdf/nihms173661.pdf

Understanding how diet influences brain health is a very important area of research. During the past two decades there has been an exponential increase in research on the gut microbiome and its roles in health and disease. Diets high in fiber are not only improve gut health but may also be beneficial for other organ systems including the brain. Gut bacteria ferment dietary fibers resulting in the production of the short-chain fatty acids (SCFAs) butyrate, propionate, and acetate. In this episode I talk with University of Leuven scientist Boushra Dalile about her research aimed at understanding if and how SCFAs affect cognition and stress responses in humans. Her experiments have shown that SCFAs attenuate neuroendocrine stress responses and butyrate in particular enhances memory. We talk about actions of butyrate mediated by interaction with cell surface receptors and nuclear histone deacetylases, as well as effects on the vagus nerve as possible mechanisms of action.

LINKS

Dalile webpage at KU Leuven

https://ppw.kuleuven.be/lbp/Bramlab/People/00115135

Boushra's Instagram on cooking for a healthy gut microbiome

https://www.instagram.com/boushracooks/

Review article on SCFAs produced by gut bacteria and their effects on the brain

https://www.nature.com/articles/s41575-019-0157-3

Perspective on prebiotics and brain health

https://pmc.ncbi.nlm.nih.gov/articles/PMC11663957/pdf/main.pdf

Original research studies discussed in this podcast

https://pmc.ncbi.nlm.nih.gov/articles/PMC7784980/pdf/41386_2020_Article_732.pdf

https://pubmed.ncbi.nlm.nih.gov/38199487/

https://pubmed.ncbi.nlm.nih.gov/38199487/

https://pubmed.ncbi.nlm.nih.gov/42557391/

The molecular machinery that translates the messenger RNAs into protein is located in ribosomes. Ribosomes are present within neurons in or near synapses, where they are particularly abundant in postsynaptic sites. Evidence suggests that local protein synthesis is required for the 'strengthening' (increased size and responsivity) of synapses that is believed to be and essential process in the encoding of memories. However, there are many different proteins that regulate protein synthesis and only recently have neuroscientists begun to provide answers the following questions: 1) how does activation of a synapse affects local protein synthesis? 2) what signaling pathways are involved? 3) what are the new proteins synthesized locally? 4) which newly produced proteins are critical for memory consolidation? 5) what are the roles of the newly synthesized proteins in memory consolidation? 6) How is synaptic activity-dependent protein synthesis altered in developmental and neurodegenerative disorders? In this episode I talk with Professor Eric Klann, Director of the Center for Neural Science at New York University, about his laboratory's contributions to the answering of these important questions.

Klann NYU page:

https://as.nyu.edu/faculty/eric-klann.html?challenge=d06e90d7-4d8f-4b88-9d8c-10b73beb60f1

Review article on protein synthesis and memory consolidation

https://pmc.ncbi.nlm.nih.gov/articles/PMC8930706/pdf/nihms-1782052.pdf

Integrated stress response and protein synthesis

https://pmc.ncbi.nlm.nih.gov/articles/PMC10964249/pdf/nihms-1970879.pdf

Neuron translatomes and memory consolidation

https://pmc.ncbi.nlm.nih.gov/articles/PMC13443933/pdf/41467_2026_Article_74455.pdf

Activity-dependent protein synthesis in neurons requires microglial-metabolic coupling.

https://pmc.ncbi.nlm.nih.gov/articles/PMC13245367/pdf/nihms-2176826.pdf

With the advent of new technological approaches and emerging discoveries has come a growing appreciation for the importance of astrocytes in neuroplasticity. In contrast to the chemical synapses between neurons, astrocytes are directly connected by gap junctions comprised of connexin proteins. In the present episode I talk with New York University neuroscientist Melissa Cooper about her research that has revealed roles for astrocyte networks in redistribution of energy substrates in response to injury. Using a clever way of molecular tagging of molecules as they pass through gap junctions in combination with whole brain imaging Melissa has identified astrocyte networks that span long distances and connect different brain regions in patterns that often do not correspond to neuron networks. We talk about the implications of her findings for roles of astrocyte networks in brain function and responses to injury and disease.

LINKS

Redistribution of metabolic resources through astrocyte networks mitigates neurodegenerative stress.:

https://pmc.ncbi.nlm.nih.gov/articles/PMC7414143/pdf/pnas.202009425.pdf

Astrocytes in the mouse brain respond bilaterally to unilateral retinal neurodegeneration.:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11929491/pdf/pnas.202418249.pdf

Astrocytes connect specific brain regions through plastic networks.:

https://pmc.ncbi.nlm.nih.gov/articles/PMC13322983/pdf/41586_2026_Article_10426.pdf

The roundworm C. Elegans has proven to be a valuable organism for advancing understanding of fundamental molecular and cellular mechanisms of aging because of its short lifespan, ease of genetic manipulations, and fully documented cellular organization. During the past 10 years or so Scott Leiser's laboratory at the University of Michigan has made several fascinating discoveries concerning how specific cells in the nervous system and elsewhere respond to environmental challenges in ways that either extend or shorten lifespan. Particularly interesting is evidence that: certain serotonergic and dopaminergic neurons that respond to food odors and availability control aging; that activation of certain touch receptors can counteract lifespan extension by dietary restriction; and that FMOs (flavin monooxygenases) extend lifespan and increase stress resistance. These findings provide new insight into the basic mechanisms of aging and for the development of interventions to extend health span.

LINKS

Leiser Laboratory:

https://medschool.umich.edu/profile/2430/scott-f-leiser

Articles discussed in this podcast

https://pmc.ncbi.nlm.nih.gov/articles/PMC9174215/pdf/41467_2022_Article_30869.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC12582246/pdf/pnas.202423780.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC11828484/pdf/elife-99971.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC12247763/pdf/nihpp-2025.05.04.652087v1.pdf

Astrocytes are known to play important roles in brain energy metabolism and the regulation of neuronal network activities. A single astrocyte has a highly elaborate and expansive morphology which enables it to interact with many thousands of neurons and synapses. Moreover, astrocytes are connected to adjacent astrocytes via gap junctions and evidence suggests that these astrocyte networks may mediate long range communications within and between brain regions. In this episode I talk with University of Montreal neuroscientist Ciaran Murphy-Royal about the rapidly expanding knowledge concerning astrocyte functions in regulating brain functions and responses to environmental conditions with a focus on stress responses. Ciaran's laboratory recently showed that astrocyte activity influences anxiety states and that selective manipulations of astrocyte activity can increase or decrease fear and anxiety. We also talk about how astrocytes may mediate chronic stress-induced memory impairment.

LINKS

Murphy-Royal laboratory:

https://www.murphyroyallab.org/

Amygdala astrocytes control anxiety states:

https://www.cell.com/neuron/fulltext/S0896-6273(26)00163-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627326001637%3Fshowall%3Dtrue

Male – female differences in astrocyte-mediated stress responses:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12246237/pdf/41467_2025_Article_61643.pdf

Early life stress, astrocyte dysfunction, and fear generalization:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11798576/pdf/elife-99988.pdf

The disease process in Alzheimer's disease involves local inflammatory processes wherein microglia are activated and produce pro-inflammatory cytokines. Accumulations of amyloid beta-peptide promote neuroinflammation by causing oxidative stress and damage to neurons and the microglia react to that damage. In this episode I talk with John Fryer about mechanisms of neuroinflammation and new immunotherapy approaches targeting amyloid in Alzheimer's disease including the use of 'nanobodies' which are small single-domain antibodies produced in camels and adapted for research and therapeutic purposes. John was previously an investigator at the Mayo Clinic and is now Director of the Center for Accelerated Nanotherapeutics in Phoenix. Note that one's risk for Alzheimer's disease is reduced by regular exercise, heart-healthy diets, and keeping intellectually and socially engaged throughout life.

LINKS

Fryer webpage at Tgen:

Articles

https://pmc.ncbi.nlm.nih.gov/articles/PMC5565413/pdf/pnas.201701137.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC13148177/pdf/nihms-2168146.pdf

https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70269

https://pmc.ncbi.nlm.nih.gov/articles/PMC13329261/pdf/ALZ-22-e71639.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC6122978/pdf/JEM_20180653.pdf