ArticleBiology of sex differences2024
TrkB-mediated sustained neuroprotection is sex-specific and Erα-dependent in adult mice following neonatal hypoxia ischemia.
Article in Biology of sex differences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 8 citations in OpenAlex.
- ERα Agonist Protects Aged Female Mice From Sevoflurane Neurotoxicity via PTEN Nuclear Translocation.CNS neuroscience & therapeutics · 2026Article
- TrkB Agonist Treatment Decreases Hippocampal Testosterone Contents in a Sex-Dependent Manner Following Neonatal Hypoxia and Ischemia.Biomolecules · 2026Article
- Acupressure Potentially Promoting the Learning and Memory Capabilities of Hypoxic Ischemic Cerebral Palsy Rats.Neural plasticity · 2026Article
- Estrogen's sex-specific effects on ischemic cell death and estrogen receptor mRNA expression in rat cortical organotypic explants.Aging brain · 2024Article
- Pharmacokinetics of 7,8-dihydroxyflavone in neonatal mice with hypoxia-ischemia related brain injury.Frontiers in pharmacology · 2024Article
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16 authors at 2 institutions in 1 country.
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Abstract
backgroundNeonatal hypoxia ischemia (HI) related brain injury is one of the major causes of life-long neurological morbidities that result in learning and memory impairments. Evidence suggests that male neonates are more susceptible to the detrimental effects of HI, yet the mechanisms mediating these sex-specific responses to neural injury in neonates remain poorly understood. We previously tested the effects of treatment with a small molecule agonist of the tyrosine kinase B receptor (TrkB), 7,8-dihydroxyflavone (DHF) following neonatal HI and determined that females, but not males exhibit increased phosphorylation of TrkB and reduced apoptosis in their hippocampi. Moreover, these female-specific effects of the TrkB agonist were found to be dependent upon the expression of Erα. These findings demonstrated that TrkB activation in the presence of Erα comprises one pathway by which neuroprotection may be conferred in a female-specific manner. The goal of this study was to determine the role of Erα-dependent TrkB-mediated neuroprotection in memory and anxiety in young adult mice exposed to HI during the neonatal period.
methodsIn this study, we used a unilateral hypoxic ischemic (HI) mouse model. Erα
resultsNeonatal DHF treatment prevented HI-induced decrements in recognition and location memory in adulthood in females, but not in males. This protective effect was absent in female mice lacking Erα. The female-specific improved recognition and location memory outcomes in adulthood conferred by DHF therapy after neonatal HI tended to be or were Erα-dependent, respectively. Interestingly, DHF triggered anxiety-like behavior in both sexes only in the mice that lacked Erα. When we assessed the severity of injury, we found that DHF therapy did not decrease the percent tissue loss in proportion to functional recovery. We additionally observed that the presence of Erα significantly reduced overall HI-associated mortality in both sexes.
conclusionsThese observations provide evidence for a therapeutic role for DHF in which TrkB-mediated sustained recovery of recognition and location memories in females are Erα-associated and dependent, respectively. However, the beneficial effects of DHF therapy did not include reduction of gross tissue loss but may be derived from the enhanced functioning of residual tissues in a cell-specific manner.
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