Student Presenter(s): Kimberly Fasciglione, Mac Josh Reandelar, Violeta B. Roumenova, Aaron T. Miller
Faculty Mentors: Gonzalo Otazu Aldana, Randy Stout, Lars Udo-Bellner, Yan Li
Department: Biomedical Sciences
School/College: College of Osteopathic Medicine, Long Island

Glial Fibrillary Acidic Protein (GFAP) is a cytoskeleton marker for astrocytes and increases upon central nervous system injury. Connexin 43 (Cx43), a gap junction protein expressed in astrocytes, regulates cognitive function, memory and epilepsy susceptibility. Cx43 forms gap junctions between astrocytes to facilitate potassium uptake and prevent neuronal hyperactivity. Cx43 aggregates (gap junction plaques at cell connections) are reduced in human autism spectrum disorder (ASD) brain tissue and in conditions of excitotoxicity and neuroinflammation (e.g. epilepsy).

ASD individuals have increased rates of seizures compared to neurotypical subjects. Children with mutant Cntnap2 gene develop a condition called cortical dysplasia focal epilepsy starting at 15 months, and can present with intractable epileptic seizures and autism. To understand the role of Cx43 in this form of ASD, we quantified GFAP and Cx43 expression in the hippocampus of 9 Cntnap2-/- mice. After administration of either compound X or saline, the hippocampus was imaged and layers CA1–CA3 were immunostained. Using intensity thresholding, we quantified the percentages of the image data that was occupied by intense Cx43 staining which represent clustered Cx43 and serve as a proxy for the amount of gap junctional coupling in astrocytes. We report preliminary results that a compound, which is currently being evaluated as a potential therapeutic, increases the expression of Cx43 with no effect on GFAP expression.