| Autor: |
Lengel D; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Program in Neuroscience, Graduate School of Biomedical Science and Professional Studies, and Drexel University College of Medicine, Philadelphia, Pennsylvania, USA., Romm ZL; Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA., Bostwick A; Department of Microbiology and Immunology, and Temple University, Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA., Huh JW; Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Snyder NW; Department of Microbiology and Immunology, and Temple University, Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA., Smith GM; Department of Neural Sciences, Temple University, Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA., Raghupathi R; Program in Neuroscience, Graduate School of Biomedical Science and Professional Studies, and Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.; Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA. |
| Abstrakt: |
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 glutamate receptor subunit expression in the DH. |
