GABAergic interneuronal loss and reduced inhibitory synaptic transmission in the hippocampal CM region after mild traumatic brain injury

被引：68

作者：

Almeida-Suhett, Camila P. ^{[1
,5
]}

Prager, Eric M. ^{[1
]}

Pidoplichko, Volodymyr ^{[2
]}

Figueiredo, Taiza H. ^{[2
]}

Marini, Ann M. ^{[1
,3
,5
]}

Li, Zheng ^{[5
,6
]}

Eiden, Lee E. ^{[5
,7
]}

Braga, Maria F. M. ^{[1
,2
,4
,5
]}

机构：

[1] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Program Neurosci, Bethesda, MD 20814 USA

[2] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA

[3] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Neurol, Bethesda, MD 20814 USA

[4] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Psychiat, Bethesda, MD 20814 USA

[5] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA

[6] NIMH, Sect Clin Studies, Intramural Res Program, Bethesda, MD 20892 USA

[7] NIMH, Sect Mol Neurosci, Intramural Res Program, Bethesda, MD 20892 USA

来源：

EXPERIMENTAL NEUROLOGY | 2015年 / 273卷

关键词：

Mild traumatic brain injury; CA1; Synaptic transmission; Controlled cortical impact; Cognitive impairment; LONG-TERM POTENTIATION; CLOSED-HEAD-INJURY; PROFESSIONAL FOOTBALL PLAYERS; CONTROLLED CORTICAL IMPACT; FLUID PERCUSSION INJURY; GABA(A) RECEPTOR; COGNITIVE DEFICITS; RETROGRADE-AMNESIA; MEMORY IMPAIRMENT; NMDA RECEPTOR;

D O I：

10.1016/j.expneurol.2015.07.028

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Patients that suffer mild traumatic brain injuries (mTBI) often develop cognitive impairments, including memory and learning deficits. The hippocampus shows a high susceptibility to mTBI-induced damage due to its anatomical localization and has been implicated in cognitive and neurological impairments after mTBI. However, it remains unknown whether mTBI cognitive impairments are a result of morphological and pathophysiological alterations occurring in the CA1 hippocampal region. We investigated whether mTBI induces morphological and pathophysiological alterations in the CA1 using the controlled cortical impact (CCI) model. Seven days after CCI, animals subjected to mTBI showed cognitive impairment in the passive avoidance test and deficits to long-term potentiation (LTP) of synaptic transmission. Deficiencies in inducing or maintaining LTP were likely due to an observed reduction in the activation of NMDA but not AMPA receptors. Significant reductions in the frequency and amplitude of spontaneous and miniature GABA(A)-receptor mediated inhibitory postsynaptic currents (IPSCs) were also observed 7 days after CCI. Design-based stereology revealed that although the total number of neurons was unaltered, the number of GABAergic interneurons is significantly reduced in the CA1 region 7 days after CCI. Additionally, the surface expression of alpha 1, beta 2/3, and gamma 2 subunits of the GABA(A) receptor were reduced, contributing to a reduced mIPSC frequency and amplitude, respectively. Together, these results suggest that mTBI causes a significant reduction in GABAergic inhibitory transmission and deficits to NMDA receptor mediated currents in the CA1, which may contribute to changes in hippocampal excitability and subsequent cognitive impairments after mTBI. Published by Elsevier Inc.

引用

页码：11 / 23

页数：13

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