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Glucocorticoid Receptor Overexpression in the Dorsal Hippocampus Attenuates Spatial Learning and Synaptic Plasticity Deficits Following Pediatric Traumatic Brain Injury
Journal article   Open access   Peer reviewed

Glucocorticoid Receptor Overexpression in the Dorsal Hippocampus Attenuates Spatial Learning and Synaptic Plasticity Deficits Following Pediatric Traumatic Brain Injury

Dana Lengel, Zoe L Romm, Anna L Bostwick, Jimmy W Huh, Nathaniel W Snyder, George Smith and Ramesh Raghupathi
Journal of neurotrauma
16 Mar 2022
DOI: https://doi.org/10.1089/neu.2022.0012
PMID: 35293260
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1089/neu.2022.0012View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

RECEPTOR MEDIATED CHANGE ELECTROPHYSIOLOGY PEDIATRIC BRAIN INJURY COGNITIVE FUNCTION
Traumatic brain injury (TBI) in children younger than 4 years old leads to long-term deficits in cognitive and learning abilities that can persist or even worsen as children age into adolescence. In this study, the role of glucocorticoid receptor (GR) function in the dorsal hippocampus (DH) in hippocampal-dependent cognitive function and synaptic plasticity were assessed following injury to the 11-day-old rat. Brain injury produced significant impairments in spatial learning and memory in the Morris water maze in male and female rats at 1-month post-injury (adolescence) which was accompanied by impairments in induction and maintenance of long-term potentiation (LTP) in the CA1 region of the DH. Brain injury resulted in a significant decrease in the expression of the glucocorticoid-inducible gene, serum- and glucocorticoid-kinase 1 (sgk1), suggestive of an impairment in GR transcriptional activity within the hippocampus. Lentiviral transfection of the human GR (hGR) in the DH improved spatial learning and memory in the Morris water maze and attenuated LTP deficits following TBI. GR overexpression in the DH was also associated with a significant increase in the mRNA expression levels of sgk1, and the glutamate receptor subunits GluA1 and GluA2 within the hippocampus. Overall, these findings support an important role of dorsal hippocampal GR function in learning and memory deficits following pediatric TBI and suggest that these effects may be related to the regulation of glutamate receptor subunit expression in the DH.

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14 citations in Web of Science
16 citations in Scopus

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Clinical Neurology
Critical Care Medicine
Neurosciences
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