Abstract

According to the two-hit hypothesis of psychoneuropathology formation, infectious diseases and other pathological conditions occurring during the critical periods of early ontogenesis disrupt normal brain development and increase its susceptibility to stress experienced in adolescence and adulthood. It is believed that these disorders are associated with changes in the functional activity of the glutamatergic system in the hippocampus. Here, we studied expression of NMDA (GluN1, GluN2a, GluN2b) and AMPA (GluA1, GluA2) glutamate receptor subunits, as well as glutamate transporter EAAT2, in the ventral and dorsal regions of the hippocampus of rats injected with LPS during the third postnatal week and then subjected to predator stress (contact with a python) in adulthood. The tests were performed 25 days after the stress. It was found that stress altered protein expression in the ventral, but not in the dorsal hippocampus. Non-stressed LPS-treated rats displayed lower levels of the GluN2b protein in the ventral hippocampus vs. control animals. Stress significantly increased the content of GluN2b in the LPS-treated rats, but not in the control animals. Stress also affected differently the exploratory behavior of LPS-injected and control rats. Compared to the non-stressed animals, stressed control rats demonstrated a higher locomotor activity during the 1st min of the open field test, while the stressed LPS-injected rats displayed lower locomotor activity than the non-stressed rats. In addition, LPS-treated stressed and non-stressed rats spent more time in the open arms of the elevated plus maze and demonstrated reduced blood levels of corticosterone. To summarize the results of our study, exposure to bacterial LPS in the early postnatal ontogenesis affects the pattern of stress-induced changes in the behavior and hippocampal expression of genes coding for ionotropic glutamate receptor subunits after psychogenic trauma suffered in adulthood.

中文翻译：

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新生儿暴露于细菌脂多糖影响心源性创伤后成年大鼠海马中离子型谷氨酸受体的行为和表达

摘要

根据心理神经病理学形成的两次打击假说，在早期个体发育的关键时期发生的传染病和其他病理状况会破坏正常的大脑发育，并增加其对青春期和成年期压力的敏感性。据信，这些疾病与海马中谷氨酸能系统的功能活性变化有关。在这里，我们研究了 NMDA（GluN1、GluN2a、GluN2b）和 AMPA（GluA1、GluA2）谷氨酸受体亚基以及谷氨酸转运蛋白 EAAT2 在第三次出生后注射 LPS 的大鼠海马腹侧和背侧区域的表达一周，然后在成年后遭受捕食者压力（与蟒蛇接触）。测试是在压力后 25 天进行的。发现压力会改变腹侧的蛋白质表达，但不会改变背侧海马体中的蛋白质表达。与对照动物相比，未受应激的 LPS 治疗的大鼠在腹侧海马体中显示出较低水平的 GluN2b 蛋白。压力显着增加了 LPS 治疗大鼠的 GluN2b 含量，但在对照动物中没有。压力还对注射 LPS 和对照大鼠的探索行为产生不同的影响。与非应激动物相比，应激对照大鼠在野外试验的第 1 分钟表现出更高的运动活性，而注射 LPS 的应激大鼠表现出低于非应激大鼠的运动活性。此外，LPS 治疗的应激和非应激大鼠在高架十字迷宫的张开臂​​上花费更多时间，并表现出降低的血液皮质酮水平。