Faculty and Staff
|Department:||Pharmacology, Physiology & Neuroscience
School of Medicine
|Phone:||803-216-3528 (office) 803-216-3517 (lab)|
Building 1, School of Medicine
Room D54 (office)
Room D53 (lab)
Building 9, Rooms 209/206 (lab)
Post Doctoral Fellowship in Age-Related Memory Loss - University of Florida
The unifying goal of research in our laboratory is to elucidate fundamental processes affiliated with neural aging and to determine their interactions with environmental, health and physiological factors that can precipitate memory loss and increase susceptibility to related neurological disorders, such as Alzheimer’s disease (AD).
How does chronic stress influence risk for memory loss and disease in aging?
Stress is an ever-present, unpredictable and, often, unavoidable feature of daily life. The hypothalamic-pituitary-adrenal (HPA) axis coordinates behavioral and cellular responses to stressful experiences via secretion of glucocorticoids. The prefrontal cortex (PFC) and hippocampus collectively express high levels of glucocorticoid receptors that impart regulatory influences upon HPA axis activity, but also render these structures susceptibl to dysregulated glucocorticoid secretion that accompanies normal aging or following chronic stress. We are investigating whether stress increases susceptibility to memory loss in aging through glucocorticoid-mediated epigenetic modifications and examining the protective effects of attenuating glucocorticoid signaling during stressful experiences across the lifespan.
Can diet build neural resilience and cognitive reserve against aging and stress?
While age-associated insulin resistance induces an overabundance of circulating glucose, the chief energy source fueling cellular respiration, glucose utilization is depressed in the aging and AD brain. However, the capacity of the brain to metabolize fat-derived ketones does not decline with age or in AD and consumption of a high fat/low carbohydrate “ketogenic” diet normalizes expression of synaptic proteins and improves cognition in aging. We are now testing the hypothesis that diet-based strategies to induce ketosis improve cognition in aging by rejuvenating synaptic mitochondria and increasing the efficiency of oxidative phosphorylation. Additionally, we are exploring whether such dietary interventions are effective in regulating glucose signaling stimulated by glucocorticoid secretion and protect against the effects of stress on brain aging and metabolic health.
Can we optimize existing pharmacotherapies for treatment of age- and stress-related impairments?
NMDA receptor (NMDAR) antagonists such as NAMENDA and esketamine are prescribed for treatment of AD and stress-related mental health disorders. However, their therapeutic mechanisms are unclear, their benefits are often temporary, and their side effects can be considerable. NMDARs are tetrameric ion channels comprised of variable subunits that determine channel properties, subcellular localization and coupling with other signaling proteins. Our lab is developing new approaches to investigate the interactions among NMDAR subunits with the goal of defining the spectrum of normal functions accomplished by various receptor configurations and to develop precision ligands that will correct NMDAR dysfunction that emerges in aging, AD and neuropsychiatric disorders.
Hernandez AR, Hernandez CM, Turckenbrod LM, Campos KT, McQuail JA, Bizon JL, Burke SN (2019) Age and ketogenic diet have dissociable effects on synapse-related gene expression between hippocampal subregions. Frontiers in Aging Neuroscience. 11:239.
McQuail JA, Krause EG, Setlow B, Scheuer DA, Bizon JL (2018) Stress-induced corticosterone release covaries with working memory in aging. Neurobiology of Aging. 71:156-160.
Hernandez AR, Hernandez CM, Campos K, Truckenbrod L, Frederico Q, Moon B, McQuail JA, Maurer AP, Bizon JL, Burke SN (2018). A ketogenic diet improves cognition and has biochemical effects in prefrontal cortex that are dissociable from hippocampus. Frontiers in Aging Neuroscience. 10: 391.
Hernandez CM, McQuail JA, Schwabe MR, Burke SN, Setlow B, Bizon JL (2018) Age-related declines in prefrontal cortical expression of metabotropic glutamate receptors that support working memory. eNeuro. 5(3). pii: ENEURO.0164-18.2018.
Hernandez AR, Hernandez CM, Campos KT, Truckenbrod LM, Sakarya Y, McQuail JA, Carter CS, Bizon JL, Maurer AP, Burke SN (2018) The anti-epileptic ketogenic diet alters hippocampal transporter levels and reduces adiposity in aged rats. Journal of Gerontology: Medical Sciences. 73(4):450-458.
Beas, BS, McQuail JA, Bañuelos C, Setlow B, Bizon JL (2017) Prefrontal cortical GABAergic signaling and impaired behavioral flexibility in aged F344 rats. Neuroscience. 345:274-286.
McQuail JA, Beas BS, Simpson K, Kelly KB, Frazier CJ, Setlow B, Bizon JL (2016) NR2A-containing NMDARs in the prefrontal cortex are required for working memory and associated with age-related cognitive decline. Journal of Neuroscience. 36(50):12537-12548.
McQuail JA, Frazier CJ, Bizon JL (2015) Molecular aspects of age-related memory decline: Role of GABA signaling. Trends in Molecular Medicine. 21(7): 450-460.
McQuail JA, Nicolle MM (2015) Spatial reference memory in normal aging Fischer 344 × Brown Norway F1 hybrid rats. Neurobiology of Aging. 36(1): 323–333.
Bañuelos C, Beas BS, McQuail JA, Gilbert RJ, Frazier CJ, Setlow B, Bizon JL (2014) Prefrontal cortical GABAergic dysfunction contributes to age-related working memory impairment. Journal of Neuroscience, 34(10): 3457-3466.