Evidence map›Paper›PMID 37720039›Full record

ArticleResearch square2023

TrkB-mediated sustained neuroprotection is sex-specific and ERα dependent in adult mice following neonatal hypoxia ischemia.

Vishal Chanana, Margaret Hackett, Nazli Deveci, Nur Aycan, Burak Ozaydin, Nur Sena Cagatay, Damla Hanalioglu, Douglas B Kintner, Karson Corcoran, Sefer Yapici and 6 more

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Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Vishal ChananaDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Margaret HackettDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Nazli DeveciDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Nur AycanDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Burak OzaydinDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Nur Sena CagatayDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Damla HanaliogluDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Douglas B KintnerDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Karson CorcoranDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Sefer YapiciDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Furkan CamciDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Jens EickhoffDepartment of Biostatistics & Medical Informatics, University of Wisconsin-Madison, Madison, WI, US.
Karyn M FrickDepartment of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
Peter FerrazanoDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
Jon E LevineDepartment of Neuroscience, University of Wisconsin-Madison, Madison, WI, USA.
Pelin CengizDepartment of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0002-5682-5664
University of Wisconsin–Madison · USUniversity of Wisconsin–Milwaukee · US

Funding

Waisman Center Intellectual and Developmental Disabilities Research CenterP50HD105353 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI Qiang Chang · 2021 to 2026
$8.5M
Collaborative Expansion of Marmoset Colonies for Neuroscience ResearchU24MH123422 · NIMH · UNIVERSITY OF WISCONSIN-MADISON · PI LEVINE, JON E, ROGERS, JEFFREY A. · 2020 to 2024
$5.1M
Neurosteroid Regulation of Adiposity, Glucose Homeostasis and Energy Expenditure in PrimatesR01DK121559 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI LEVINE, JON E · 2019 to 2023
$3.0M
Mechanisms underlying memory regulation by 17beta-estradiol, canonical Wnt signaling, and BDNF in male and female miceR01MH107886 · NIMH · UNIVERSITY OF WISCONSIN MILWAUKEE · PI FRICK, KARYN M · 2016 to 2020
$1.9M
Sex Differences in Neurotrophin Mediated Neonatal Neuroprotection: Role of ER AlphaR01NS111021 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI CENGIZ, PELIN · 2019 to 2023
$1.7M
Estrogen receptors and TrkB mediated neuroprotection in neonatal hypoxia-ischemiaK08NS088563 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI CENGIZ, PELIN · 2015 to 2019
$994k
Age-dependent microglial responses in hypoxia-ischemiaK08NS078113 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI FERRAZZANO, PETER A · 2013 to 2017
$967k
Whole exome analyses in naturally occurring hyperandrogenic female monkeysR21HD102172 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI ABBOTT, DAVID H, LEVINE, JON E · 2020 to 2021
$400k
NICHD NIH HHS P50 HD105353NICHD NIH HHS R21 HD102172NIDDK NIH HHS R01 DK121559NIMH NIH HHS R01 MH107886NIMH NIH HHS U24 MH123422NINDS NIH HHS K08 NS078113NINDS NIH HHS K08 NS088563NINDS NIH HHS R01 NS111021
6 · The paper itself

Abstract

Background: Neonatal 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. Methods: In this study we used a unilateral hypoxic ischemic (HI) mouse model. ERα Results: Neonatal 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. Thus, the female-specific and ERα-dependent neuroprotection conferred by DHF therapy after neonatal HI was associated with improved learning and memory outcomes in adulthood. 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. Conclusions: These observations provide evidence for a therapeutic role for DHF in which sustained recovery of memory in females is TrkB-mediated and ERα-dependent. 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.

Indexed as

7,8-dihydroxyflavonebrain injuryDHFestrogen receptorhypoxiahypoxic ischemic encephalopathyischemianeonateSex differencesTrkBtyrosine kinase B

Identifiers

PMID37720039
PMCPMC10503864
OpenAlexW4386525817

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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.