I grew up in East Tennessee and completed my BA in Economics at the University of Georgia. As an undergraduate, I worked in a behavioral neuropharmacology lab studying the cognitive effects of the chemical contraceptives ethinyl estradiol and levonorgestrel. Now, I study astrocyte activation in Alzheimer's disease.
My doctoral work is designed to expand knowledge of the in vivo functioning of astrocytes in the context of AD-like pathology with a major focus on astrocytic excitatory amino acid transporters (EAATs). Astrocytic EAATs remove glutamate from the extracellular milieu and provide a primary defense against excitotoxic damage to synapses. Metabolically, EAATs couple synaptic glutamatergic activity to key electrochemical gradients that promote glucose utilization and glycolysis in astrocytes, leading to the release of lactate, the primary energy substrate for neurons. EAATs may also ameliorate excitotoxic damage to the structural barrier between vascular endothelium and perivascular astrocyte endfeet. The predominant EAAT, EAAT2 (rodent homolog glutamate transporter 1, Glt-1), accounts for the majority of glutamate uptake. Loss of EAAT2/Glt-1 is an early feature of AD that continues to diminish with worsening AD pathology. Normalization of Glt-1, by genetic overexpression or treatment with pharmacological agents that enhance its function, protects synaptic proteins, improves basal synaptic strength, and improves cognition. We hypothesize that upregulating astrocytic Glt-1 will mitigate AD pathology by improving lactate metabolism, restoring neurovascular function, and alleviating glutamate-mediated hyperexcitability.
Sanders-Brown Center on Aging T32
Professional Student Mentored Research Fellowship
- Simone, J.; Bogue, EA ; Bhatti, DL ; Day, LE ; Farr, NA ; Grossman, AM ; Holmes, PV "Ethinyl estradiol and levonorgestrel alter cognition and anxiety in rats concurrent with a decrease in tyrosine hydroxylase expression in the locus coeruleus and brain-derived neurotrophic factor expression in the hippocampus." Psychoneuroendocrinology 62, (2015): 265-78. [PubMed Link] | [ Full text ]