ArticleeNeuro
ERα Signaling Is Required for TrkB-Mediated Hippocampal Neuroprotection in Female Neonatal Mice after Hypoxic Ischemic Encephalopathy(1,2,3).
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- TrkB Agonist Treatment Decreases Hippocampal Testosterone Contents in a Sex-Dependent Manner Following Neonatal Hypoxia and Ischemia.Biomolecules · 2026Article
- Stress-induced epigenome changes as a risk factor in the onset of mental disorders.Frontiers in psychiatry · 2026Review
- Sex Steroids and Brain-Derived Neurotrophic Factor Interactions in the Nervous System: A Comprehensive Review of Scientific Data.International journal of molecular sciences · 2025Review
- Mitochondrial Calcium Uniporter (MCU) is Involved in an Ischemic Postconditioning Effect Against Ischemic Reperfusion Brain Injury in Mice.Cellular and molecular neurobiology · 2024Article
- TrkB-mediated neuroprotection in female hippocampal neurons is autonomous, estrogen receptor alpha-dependent, and eliminated by testosterone: a proposed model for sex differences in neonatal hippocampal neuronal injury.Biology of sex differences · 2024Article
- TrkB-mediated sustained neuroprotection is sex-specific and Erα-dependent in adult mice following neonatal hypoxia ischemia.Biology of sex differences · 2024Article
- Pharmacokinetics of 7,8-dihydroxyflavone in neonatal mice with hypoxia-ischemia related brain injury.Frontiers in pharmacology · 2024Article
- Selectively compromised inner retina function following hypoxic-ischemic encephalopathy in mice: A noninvasive measure of severity of the injury.Neurochemistry international · 2023Article
- Retinal vascular recovery revealed by retinal imaging following neonatal hypoxia ischemia in mice: Is there a role for tyrosine kinase receptor modulation?Brain research · 2022Article
- Review
- A TrkB agonist prodrug prevents bone loss via inhibiting asparagine endopeptidase and increasing osteoprotegerin.Nature communications · 2022Article
- Novel Injury Scoring Tool for Assessing Brain Injury following Neonatal Hypoxia-Ischemia in Mice.Developmental neuroscience · 2022Article
- Estrogen receptor α: a critical role in successful female cognitive aging.Climacteric : the journal of the International Menopause Society · 2021Article
- Src Family Kinases Inhibition Ameliorates Hypoxic-Ischemic Brain Injury in Immature Rats.Frontiers in cellular neuroscience · 2021Article
- Effects of Melatonin on Neurobehavior and Cognition in a Cerebral Palsy Model ofFrontiers in endocrinology · 2021Article
- Aggravated brain injury after neonatal hypoxic ischemia in microglia-depleted mice.Journal of neuroinflammation · 2020Article
- Developmental differences in microglia morphology and gene expression during normal brain development and in response to hypoxia-ischemia.Neurochemistry international · 2019Article
- Sex differences in Hippocampal Memory and Learning following Neonatal Brain Injury: Is There a Role for Estrogen Receptor-α?Neuroendocrinology · 2019Review
- A combination antioxidant therapy to inhibit NOX2 and activate Nrf2 decreases secondary brain damage and improves functional recovery after traumatic brain injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Article
- Tanshinone IIA improves hypoxic ischemic encephalopathy through TLR‑4‑mediated NF‑κB signal pathway.Molecular medicine reports · 2018Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Male neonate brains are more susceptible to the effects of perinatal asphyxia resulting in hypoxia and ischemia (HI)-related brain injury. The relative resistance of female neonatal brains to adverse consequences of HI suggests that there are sex-specific mechanisms that afford females greater neuroprotection and/or facilitates recovery post-HI. We hypothesized that HI preferentially induces estrogen receptor α (ERα) expression in female neonatal hippocampi and that ERα is coupled to Src family kinase (SFK) activation that in turn augments phosphorylation of the TrkB and thereby results in decreased apoptosis. After inducing the Vannucci's HI model on P9 (C57BL/6J) mice, female and male ERα wild-type (ERα(+/+)) or ERα null mutant (ERα(-/-)) mice received vehicle control or the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF). Hippocampi were collected for analysis of mRNA of ERα and BDNF, protein levels of ERα, p-TrkB, p-src, and cleaved caspase 3 (c-caspase-3) post-HI. Our results demonstrate that: (1) HI differentially induces ERα expression in the hippocampus of the female versus male neonate, (2) src and TrkB phosphorylation post-HI is greater in females than in males after 7,8-DHF therapy, (3) src and TrkB phosphorylation post-HI depend on the presence of ERα, and (4) TrkB agonist therapy decreases the c-caspase-3 only in ERα(+/+) female mice hippocampus. Together, these observations provide evidence that female-specific induction of ERα expression confers neuroprotection with TrkB agonist therapy via SFK activation and account for improved functional outcomes in female neonates post-HI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.