Blast-Induced Mild Traumatic Brain Injury Alterations of Corticotropin-Releasing Factor Neuronal Activity in the Mouse Hypothalamic Paraventricular Nucleus.
Blast-Induced Mild Traumatic Brain Injury Alterations of Corticotropin-Releasing Factor Neuronal Activity in the Mouse Hypothalamic Paraventricular Nucleus.
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DOI：
10.3389/fnsyn.2021.804898
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发表时间：
2021
影响因子：
3.7
通讯作者：
Nugent FS
中科院分区：
文献类型：
--
作者：
Simmons S;Langlois LD;Oyola MG;Gouty S;Wu TJ;Nugent FS
爆炸引起的轻度创伤性脑损伤 (mbTBI) 是美国军人和退伍军人 TBI 的最常见原因。那些暴露于 TBI 的人患神经精神疾病的风险更大，例如创伤后应激障碍、焦虑和抑郁症以及 TBI 后的物质使用障碍。此前，我们已经证明 mbTBI 会增加小鼠的焦虑样行为，并调节室旁核 (PVN) 促肾上腺皮质激素释放因子 (CRF) 神经元水平的压力。为了扩展 mTBI 如何集中调节应激轴，这里使用损伤后 7 天的假手术小鼠和 mbTBI 成年雄性 CRF:tdTomato 小鼠的下丘脑切片中的全细胞膜片钳记录来评估 PVN CRF 神经元活动。我们发现 mbTBI 一般不会影响 PVN CRF 神经元的神经元兴奋性和内在膜特性；这种损伤选择性地增加了位于背侧 PVN (dPVN) 但不是腹侧 PVN (vPVN) 的 PVN CRF 神经元自发神经元放电的频率。一致地，mbTBI 诱导的 dPVN CRF 过度活跃与 dPVN CRF 神经元上自发 GABA 能传输的突触前和突触后抑制相关，这表明 mbTBI 诱导的 GABA 能突触功能障碍可能是 dPVN CRF 神经元过度活跃和 dPVN CRF 信号传导增加的基础。目前的结果为 mbTBI 诱导的 PVN CRF 神经元活动和 GABA 突触功能的改变提供了第一个证据，这些改变可能介导 mbTBI 后下丘脑 CRF 失调，导致与爆炸损伤相关的应激精神病理学。
Blast-induced mild traumatic brain injury (mbTBI) is the most common cause of TBI in US service members and veterans. Those exposed to TBI are at greater risk of developing neuropsychiatric disorders such as posttraumatic stress disorder, anxiety and depressive disorders, and substance use disorders following TBI. Previously, we have demonstrated that mbTBI increases anxiety-like behaviors in mice and dysregulates stress at the level of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN). To expand on how mTBI may dysregulate the stress axis centrally, here PVN CRF neuronal activity was evaluated using whole cell-patch clamp recordings in hypothalamic slices from sham and mbTBI adult male CRF:tdTomato mice 7 days post-injury. We found that mbTBI generally did not affect the neuronal excitability and intrinsic membrane properties of PVN CRF neurons; this injury selectively increased the frequency of spontaneous neuronal firing of PVN CRF neurons localized to the dorsal PVN (dPVN) but not ventral PVN (vPVN). Consistently, mbTBI-induced dPVN CRF hyperactivity was associated with pre- and post-synaptic depression of spontaneous GABAergic transmission onto dPVN CRF neurons suggesting that mbTBI-induced GABAergic synaptic dysfunction may underlie dPVN CRF neuronal hyperactivity and increases in dPVN CRF signaling. The present results provide the first evidence for mbTBI-induced alterations in PVN CRF neuronal activity and GABAergic synaptic function that could mediate hypothalamic CRF dysregulation following mbTBI contributing to stress psychopathology associated with blast injury.
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影响因子：
3.4
作者：
Langlois LD;Berman RY;Shepard RD;Simmons SC;Tsuda MC;Gouty S;Choi KH;Nugent FS
通讯作者：
Nugent FS
影响因子：
3.7
作者：
Wamsteeker Cusulin JI;Füzesi T;Watts AG;Bains JS
通讯作者：
Bains JS
影响因子：
3.3
作者：
Russell, Ashley L.;Handa, Robert J.;Wu, T. John
通讯作者：
Wu, T. John
影响因子：
3.8
作者：
Wong, Eunice C.;Schell, Terry L.;Miles, Jeremy N. V.
通讯作者：
Miles, Jeremy N. V.
影响因子：
2.5
作者：
Qiu, DL;Chu, CP;Kannan, H
通讯作者：
Kannan, H