Cited by 14Traumatic Brain Injury and Neurovascular DisturbancesMemory and Neural MechanismsTraumatic Brain Injury Research

Glucocorticoid receptor overexpression in the dorsal Hippocampus attenuates spatial learning and synaptic plasticity deficits after pediatric traumatic brain injury

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Lengel, Dana, Romm, Zoe L., Bostwick, Anna, Huh, Jimmy W., Snyder, Nathaniel W., Smith, George M., Raghupathi, Ramesh·2022·Journal of Neurotrauma

Abstract

Traumatic brain injury (TBI) in children <4 years of age leads to long-term deficits in cognitive and learning abilities that can persist or even worsen as these 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 for dorsal hippocampal GR function in learning and memory deficits following pediatric TBI and suggest that these effects may be related to the regulation of glutamat…

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Crossref · 10.1089/neu.2022.0012

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  • Overexpression of SGK1 receptors in the dorsal hippocampus enhances memory, correlating with increased expression of SGK1 and mRNA of hippocampal glutamate receptor subunits GluA1 and GluA2.

    “Overexpression of SGK1 receptors in the dorsal hippocampus enhances memory, which correlates with a significant increase in the expression of SGK1 and the mRNA of hippocampal glutamate receptor subunits GluA1 and GluA2”

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Authors
Lengel, D., Romm, Z. L., Bostwick, A., Huh, J. W., Snyder, N. W., Smith, G. M., & Raghupathi, R.
Affiliations
  • Drexel University (US)
  • Temple University (US)
  • Children's Hospital of Philadelphia (US)
Corresponding author
Raghupathi, Ramesh
Venue
Journal of Neurotrauma
Published
2022-06-28
Volume
39
Issue
13-14
Pages
979-998
ISSN
  • 0897-7151 (ISSN-L)
  • 1557-9042
OpenAlex
W4220862725
Cited by
14
References
62
Citations by year
2025: 2 · 2024: 7 · 2023: 3 · 2022: 2
FWCI
1.84
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurotrauma (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS110898)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
glucocorticoid receptor, pediatric traumatic brain injury, dorsal hippocampus, spatial learning and memory, synaptic plasticity, long-term potentiation, SGK1, glutamate receptor subunits, GluR1, GluA2
MeSH terms
Brain Injuries, Traumatic, Animals, Brain Injuries, Child, Female, Glucocorticoids, Hippocampus, Humans, Male, Neuronal Plasticity, Receptors, Glucocorticoid, Receptors, Glutamate, Long-Term Potentiation, Maze Learning, Rats, Spatial Learning

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