Neuroprotection by estrogen on hypoglycemic injury on hypothalamic cells at the cellular and molecular level

Glucose is the main metabolic fuel of the brain and its availability is directly linked to neuronal activity. Recurrent episodes of hypoglycemia can result in loss of neurons, impaired IQ and can ultimately lead to morbidity. In the present study we have reported the neuroprotection of estrogen on hypoglycemic injury in hypothalamic cell line. The cell viability and proliferation was determined under various conditions. There was a marked decrease in the cell count when exposed to hypoglycemia and the cell count increased when treated with estrogen (42.8 vs 98.5, 24 hours, p<0.0001). Under hypoglycemic conditions within 24 hours there was a significant loss in mitochondrial function with ~80% of retrieval in the presence of estrogen. The attenuation of the death pathways was only seen within the first 24 hours and gradually decreased with time. DNA microarray studies showed AKT, a promoter of cell survival, was down‐regulation in the absence of glucose and in the presence of estrogen an increase in gene expression. Glycogen synthase kinase beta (GSK3b) showed the reverse effect. Taking together the biochemical and molecular data it seems that one of the mechanism by which estrogen shows its neuroprotection is through the Akt‐GSK3b pathway activation.