Neuroprotective effect of estrogen on hypoglycemic injury in hypothalamic mouse cells (767.6)

Abstract

Glucose is the main metabolic fuel of the brain. Recurrent episodes of hypoglycemia can lead to seizures, coma, and even death. The hypothalamus; a region involved in feeding and energy balance is most vulnerable to this injury. In the present study we report neuroprotection of estrogen on hypoglycemic injury in a hypothalamic cell line. The cell viability, toxicity and proliferation were determined using MTT, lactate dehydrogenase (LDH) assay, and cell count. There was a significant increase in the cell count and increase in mitochondrial function in the presence of estrogen (p<0.0001) when exposed to hypoglycemia within 24 hours. The attenuation of the death pathways was only seen within the first 24 hours and gradually decreased with time. Percent cytotoxicity also increased in the absence of glucose and decreased in the presence of estrogen within 24 hours. Two pathways seemed viable in mediating estrogen action, the phospho‐AKT pathway, and a pathway involving caveolin‐1 (CAV‐1). In order to determine estrogen mode of action, PRAS 40 was analyzed via ELISA assay, which showed no change when exposed to hypoglycemic shock. This suggested that the phospho‐AKT pathway was not involved in estrogen mode of action. Our current efforts are focused on determining whether estrogen neuroprotection is mediated through CAV‐1 and re‐testing the phospho‐AKT pathway via western blot analysis.