Sex differences in hippocampal memory and learning following neonatal brain injury: Is there a role for ER α?

Neonatal encephalopathy due to hypoxia ischemia (HI) leads to severe, life-long morbidities in thousands of neonates born in the US and worldwide each year. Varying capacities of long-term episodic memory, verbal working memory and learning can present without cerebral palsy and have been associated with the severity of neonatal encephalopathy sustained at birth. Among children who sustain a moderate degree of HI at birth, girls have larger hippocampal volumes compared to boys. Clinical studies indicate that female neonatal brains are more resistant to the effects of neonatal HI, resulting in better long-term cognitive outcomes as compared to males with comparable brain injury. Our most recent mechanistic studies have addressed the origins and cellular basis of sex differences in hippocampal neuroprotection following neonatal HI-related brain injury, and implicate estrogen receptor α(ERα) in the neurotrophin receptor-mediated hippocampal neuroprotection in female mice. This review summarizes the recent findings on ERα dependent, neurotrophin-mediated hippocampal neuroprotection, and weighs the evidence that this mechanism plays an important role in preserving long-term mem ory and learning following HI in females.
Source: Neuroendocrinology - Category: Endocrinology Source Type: research