Brain Ponderings podcast with Dr. Mark Mattson

This year the Nobel Prize in physiology or medicine was awarded to three scientists for optogenetics – a method for activating or inhibiting neurons with light. In this episode I talk with UC Berkeley scientist Miriam Morales about magnetogenetic technologies being developed to enable activation or inhibition of specific neurons in the brain with magnetic fields as a means of understanding how the...

Growth hormone (GH) is produced by cells in the pituitary gland and released into the blood where it travels to the liver and therein stimulates the production of insulin-like growth factor 1 (IGF1). The release of GH which occurs in a pulsatile manner is controlled by neurons in the brain. The GH – IGF1 neuroendocrine system is critical for normal growth of the body during development. During his...

Tumor necrosis factor (TNF) is a pro-inflammatory cytokine known for its detrimental effects on tissues in disease such as rheumatoid arthritis, Crohn's disease, and skin psoriasis. However, TNF has normal functions in the absence of inflammation. TNF is produced in low amounts by cells in the brain – particularly microglia and astrocytes – and neurons can respond to TNF in several ways. In this e...

Cells have evolved elaborate and highly-coordinated ways of responding to the stresses they encounter in the course of their normal functions and in response to environmental challenges. Research is revealing the that mitochondria are a hub of adaptive cellular stress responses. Mitochondria sense oxidative, metabolic, and ionic stress and then triggers an integrated adaptive stress response. In t...

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 va...

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 contribut...

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...

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 enco...

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 t...

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 spe...

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 medi...

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 immunoth...

While it has long been known that activity in neural networks in sleep differs from activity during waking hours. EEG recordings have revealed patterns of activity oscillations associated with deep (non-REM) sleep and rapid eye movement (REM) sleep. However, it remains unclear how transitions from wake to sleep and from sleep to wake are controlled. One hypothesis is that there are sleep-inducing...

In this episode I talk with Weill Cornell Medicine professor Tim Ryan about the local regulation of energy metabolism in synapses.   Tim and his colleagues use high resolution imaging of fluorescent probes that enable measurements of ATP and calcium in presynaptic terminals and postsynaptic dendrites of neurons in which energy substrates are manipulated. His lab has made several novel findings tha...

In Alzheimer's disease and other 'Tauopathies' the Tau protein (which normally controls the polymerization of microtubules) becomes hyperphosphorylated and self-aggregates into insoluble fibrils called 'neurofibrillary tangles' within neurons. Excessive phosphorylation of Tau by a kinase called GSK3 is implicated in neurofibrillary tangle formation and neuron death in Alzheimer's disease. The Span...

Ultraprocessed foods that contain high amounts of simple sugars (particularly high-fructose corn syrup), saturated fats, salt, and various chemicals that enhance taste and color. In this episode I talk with University of Michigan psychology professor Ashley Gearhardt about research showing that ultraprocessed foods are addictive and a major cause of poor metabolic health and chronic diseases in th...

In this episode – a role reversal. Mark is interviewed by Justin Lathia a professor at the Cleveland Clinic and former graduate student in Mark's lab. The podcast provides a whirlwind tour of Mark's early life and research career – from graduate and postdoc training in Iowa and Colorado, to research in his laboratories at the University of Kentucky and the National Institute on Aging. Justin also...

The combined efforts of neurologists, geneticists, molecular biologists, and electrophysiologists have identified genes in which rare mutations cause either extreme pain sensitivity or complete lack of pain sensation. The extreme pain syndromes include primary erythromelalgia and small fiber neuropathies that result painful extremities triggered pressure, touch, and heat. Three of these genes enco...

Optimal health depends critically on maintenance of an evolutionarily ancient circadian clock that ticks within all cells of the body and brain. Discovery of the genes that encode the core proteins of the molecular clock have revealed how the clock works and, importantly, how the clock influences health and resilience. Joseph Takahashi discovered the gene for CLOCK which is one of four proteins th...

In this episode I talk with MIT neuroscientist Ev Fedorenko about the neural networks that process language in the human brain, the relationships between the processing of language and thought, evolutionary perspectives on thinking versus communicating, and artificial intelligence systems as tools for advancing understanding of the neurobiology of language. To understand the neural networks of lan...

Vision loss is a major cause of disability throughout the world. While there are effective treatments for cataracts and for preventing glaucoma, there are numerous genetic disorders that cause degeneration of cells in the retina for which no treatments currently exist. Inherited retinal diseases can be caused by recessive (loss-of function) or dominant (gain-of-function) mutations in genes express...

It is well-established that neurons have a high energy (ATP) demand and that mitochondrial impairment can render neurons vulnerable to degeneration. However, surprisingly little is known about the involvement of mitochondria in the activation and plasticity of individual synapses. In this episode Vidhya Rangaraju, head of the Neuroenergetics Laboratory at the Max Planck Florida Institute for Neuro...

How does the brain rapidly integrate information coming our different senses with stored information, and their saliences, so as to make decisions and respond (or not)?   In this episode I talk with UCLA Professor Lucina Uddin who investigates the relationships between connectivity of different brain regions and cognition with an emphasis on brain development and disorders thereof. In this episode...

The amyloid precursor protein (APP) is a transmembrane protein and the source of the amyloid beta-peptide that accumulates in plaques in the brain in Alzheimer's disease. However, the normal function(s) of APP are uncertain. In this episode I talk with Bassem Hassan, a developmental neurobiologist and molecular biologist at the Paris Brain Institute who has made major contributions that advance an...