Glucocorticoid Receptor Overexpression in the Dorsal Hippocampus Attenuates Spatial Learning and Synaptic Plasticity Deficits after Pediatric Traumatic Brain Injury.
Glucocorticoid Receptor Overexpression in the Dorsal Hippocampus Attenuates Spatial Learning and Synaptic Plasticity Deficits after Pediatric Traumatic Brain Injury.
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背海马体中糖皮质激素受体的过度表达会减弱小儿创伤性脑损伤后的空间学习和突触可塑性缺陷。
DOI：
10.1089/neu.2022.0012
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发表时间：
2022
影响因子：
4.2
通讯作者：
Raghupathi,Ramesh
中科院分区：
文献类型：
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作者：
Lengel,Dana;Romm,ZoeL;Bostwick,Anna;Huh,JimmyW;Snyder,NathanielW;Smith,GeorgeM;Raghupathi,Ramesh
4岁以下儿童的创伤性脑损伤（TBI）会导致认知和学习能力的长期缺陷，这些缺陷可能持续存在，甚至随着这些儿童进入青春期而恶化。本研究评估了11日龄大鼠损伤后海马背侧糖皮质激素受体（GR）功能在海马依赖认知功能和突触可塑性中的作用。脑损伤后1个月（青春期），雄性和雌性大鼠Morris水迷宫的空间学习和记忆出现明显的损伤，并伴有DH CA1区长时程增强（LTP）的诱导和维持功能的损伤。脑损伤导致糖皮质激素诱导基因、血清糖皮质激素激酶1和糖皮质激素激酶1 （sgk1）的表达显著降低，提示海马内GR转录活性受损。慢病毒转染DH中的人GR （hGR）可改善Morris水迷宫中的空间学习和记忆，并减轻TBI后LTP缺陷。DH中GR过表达还与海马内sgk1、谷氨酸受体亚基GluA1和GluA2 mRNA表达水平显著升高相关。总之，这些发现支持海马背侧GR功能在儿童TBI后的学习和记忆缺陷中的重要作用，并提示这些作用可能与DH中谷氨酸受体亚基表达的调节有关。
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.