Sex differences in Hippocampal Memory and Learning following Neonatal Brain Injury: Is There a Role for Estrogen Receptor-alpha?

Zafer D., Aycan N., Ozaydin B., Kemanli P., Ferrazzano P., Levine J. E., ...More

NEUROENDOCRINOLOGY, vol.109, no.3, pp.249-256, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 109 Issue: 3
  • Publication Date: 2019
  • Doi Number: 10.1159/000499661
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.249-256
  • Keywords: Neonate, Estrogen receptor-alpha, Sex differences, Hippocampus, Hypoxia-ischemia, Encephalopathy, Tyrosine kinase receptor, ESTRADIOL-MEDIATED PROTECTION, NEUROTROPHIC FACTOR, DEPENDENT NEUROPROTECTION, HYPOXIA-ISCHEMIA, BDNF PROTECTS, TRKB RECEPTOR, CA1 NEURONS, 7,8-DIHYDROXYFLAVONE, ACTIVATION, MODEL
  • Van Yüzüncü Yıl University Affiliated: No


Neonatal encephalopathy due to hypoxia-ischemia (HI) leads to severe, life-long morbidities in thousands of neonates born in the USA 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 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-alpha (ER alpha) in the neurotrophin receptor-mediated hippocampal neuroprotection in female mice. This review summarizes the recent findings on ER alpha-dependent, neurotrophin-mediated hippocampal neuroprotection and weighs the evidence that this mechanism plays an important role in preservation of long-term memory and learning following HI in females.