Reduced hippocampus volume in the mouse model of Posttraumatic Stress Disorder
Reduced hippocampus volume in the mouse model of Posttraumatic Stress Disorder
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DOI：
10.1016/j.jpsychires.2010.10.014
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发表时间：
2011-05-01
影响因子：
4.8
通讯作者：
Wotjak, Carsten T.
中科院分区：
文献类型：
--
作者：
Golub, Yulia;Kaltwasser, Sebastian F.;Wotjak, Carsten T.
一些（但不是所有）针对创伤后应激障碍 (PTSD) 患者的研究报告称，海马体 (HPC) 体积减少。特别是，目前尚不清楚较小的海马体积是否代表了 PTSD 的易感因素，而不是创伤的结果。为了深入了解大脑形态和创伤暴露之间的关系，我们通过体内锰增强磁共振成像 (MEMRI) 和离体超显微测量研究了 PTSD 小鼠模型中 HPC 的体积和分子变化。两个月后，短暂的、不可避免的脚部震动导致左 HPC 和右中央杏仁核的体积减少。这种体积损失反映在 HPC 中生长相关蛋白 43 (GAP43) 的下调。丰富的住房降低了与创伤相关的背景恐惧的强度，无论它是在休克之前还是之后提供的。除此之外，丰富的住房导致颅内体积增加，包括侧脑室和海马体，并导致 GAP43 上调（如 MEMRI 和蛋白质印迹分析所示），从而部分补偿了创伤相关的 HPC 体积损失和 GAP43 表达下调。这些数据共同表明，小鼠的创伤经历导致 HPC 和中央杏仁核体积减少，可能是由于轴突突起的收缩所致。丰富的住房可能会引起营养变化，这可能有助于在行为、形态和分子水平上改善与创伤相关的 PTSD 样症状。 (C) 2010 Elsevier Ltd. 保留所有权利。
Some, but not all studies in patients with posttraumatic stress disorder (PTSD), report reduced hippocampus (HPC) volume. In particular it is unclear, whether smaller hippocampal volume represents a susceptibility factor for PTSD rather than a consequence of the trauma. To gain insight into the relationship of brain morphology and trauma exposure, we investigated volumetric and molecular changes of the HPC in a mouse model of PTSD by means of in vivo Manganese Enhanced Magnetic Resonance Imaging (MEMRI) and ex vivo ultramicroscopic measurements. Exposure to a brief inescapable foot shock led to a volume reduction in both left HPC and right central amygdala two months later. This volume loss was mirrored by a down-regulation of growth-associated protein-43 (GAP43) in the HPC. Enriched housing decreased the intensity of trauma-associated contextual fear, independently of whether it was provided before or after the shock. Beyond that, enriched housing led to an increase in intracranial volume, including the lateral ventricles and the hippocampus, and to an up-regulation of GAP43 as revealed by MEMRI and Western blot analysis, thus partially compensating for trauma-related HPC volume loss and down-regulation of GAP43 expression. Together these data demonstrate that traumatic experience in mice causes a reduction in HPC and central amygdala volume possibly due to a shrinkage of axonal protrusions. Enriched housing might induce trophic changes, which may contribute to the amelioration of trauma-associated PTSD-like symptoms at behavioural, morphological and molecular levels. (C) 2010 Elsevier Ltd. All rights reserved.