Bistra Nankova

Dr. Nankova is an Associate Professor in Pediatrics, Biochemistry and Molecular Biology at New York Medical College and Director of the Developmental Neuroscience Research Laboratory.

She is a member of the Society for Neuroscience and the NYMC Radiation Safety Committee (2007-09).

The major focus of the laboratory is regulation of neurotransmitter-related genes with particular interest in the role of diet-derived short chain fatty acids (SCFA) in normal human physiology and disease. Blood levels of SCFA-like butyrate arise primarily from ingesting complex carbohydrates that are later fermented by bacteria normally present in the intestine. These fermentation byproducts get absorbed into the blood stream in levels sufficient to alter gene expression in remote tissues throughout the body, including peripheral and central nervous system. At birth, bacterial flora are typically acquired from the mother and may vary in type or amount throughout life depending on diet, ingested organisms, or use of antibiotics. At least three categorical processes are involved in creating the biological effects of SCFA: chromatin remodeling, cis- and trans-acting butyrate-dependent factors that regulate transcription of specific genes, and regulation of mRNA stability.

We have shown that the production of the neurotransmitters dopamine, epinephrine, and norepinephrine is affected by SCFA in a dose-dependent manner in a tissue culture cell model. Given the higher incidence of autism after intrauterine exposure to elevated plasma SCFA following ethanol consumption, valproate therapy, or in infants of diabetic women, and the elevated monoamine concentration in the brain and blood of ASD patients, we hypothesized that SCFA may directly influence brain catecholaminergic pathways. In collaboration with Dr. Derrick MacFabe of The Kilee Patchell-Evans Autism Research Group, University of Western Ontario, we are developing an animal model of autism to enable detection of ASD-relevant genetic networks regulated by SCFA and help identify potential novel targets for clinical intervention and future research. The studies employ a multidisciplinary approach using behavioral, biochemical, recombinant genetics, and genome-wide expression profiling techniques.

Another venue of investigation relates to hypoglycemia associated autonomic failure (HAAF), a frequent complication of insulin-dependent diabetic patients, characterized by attenuated sympathoadrenal responses to falling plasma glucose concentrations induced by recurrent hypoglycemia. The clinical impact of HAAF, including its reversal by avoidance of hypoglycemia, is well established, but its mechanisms are largely unknown. Our prior observations suggested that elevated SCFA alone or in combination with trans-synaptic activity may down regulate catecholamine biosynthesis and content; an interpretation consistent with the failure of the adrenal medulla to release epinephrine as a compensation for the low blood sugar following recurrent episodes of hypoglycemia typical of HAAF. Since changes in fatty acid metabolism occur as part of the counter-regulatory responses to hypoglycemia, we will examine whether modulation cholinergic neurotransmission by partial nicotinic receptor agonists may preserve the epinephrine responses during hypoglycemia yielding important public health implications as translational therapy.