Chronic hypothalamic-pituitary-adrenal axis disruption alters glutamate homeostasis and neural responses to stress in male C57Bl6/N mice.
Chronic hypothalamic-pituitary-adrenal axis disruption alters glutamate homeostasis and neural responses to stress in male C57Bl6/N mice.
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慢性下丘脑-垂体-肾上腺轴破坏改变雄性C57 B16/N小鼠谷氨酸稳态和应激神经反应
DOI：
10.1016/j.ynstr.2022.100466
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发表时间：
2022-07
影响因子：
5
通讯作者：
Karatsoreos, Ilia N.
中科院分区：
文献类型：
--
作者：
Kinlein, Scott A.;Wallace, Naomi K.;Savenkova, Marina, I;Karatsoreos, Ilia N.
现在已经确定的是，压力会引起大脑和身体的生理变化，并对健康的许多方面产生重大影响。下丘脑-垂体-肾上腺（HPA）轴是介导应激综合反应的主要神经内分泌系统。HPA活动的适当参与和终止可提高生存率并优化对压力的生理和行为反应，而该系统的功能障碍与负面健康结果有关，如抑郁，焦虑和创伤后应激障碍。谷氨酸信号在整个大脑中与压力相关的信息的传递中起着重要作用。此外，异常的谷氨酸信号传导对神经可塑性和突触功能具有负面影响，并且与应激相关的病理学有关。然而，HPA功能障碍和谷氨酸信号传导之间的联系尚未完全了解。我们测试了HPA轴功能障碍（在饮用水中使用低剂量的慢性皮质酮）如何影响雄性C57 BL/6 N小鼠在基线和急性应激下的谷氨酸稳态和神经反应。使用激光显微切割和转录组学分析，我们表明，HPA轴的慢性中断改变了内侧前额叶皮层（mPFC），海马和杏仁核中谷氨酸信号相关基因的表达。虽然在我们的HPA功能障碍模型中，海马和杏仁核对压力的神经反应（通过FOS测量）没有受到影响，但我们观察到mPFC对压力的反应过度。为了进一步探讨这一点，我们进行了在体内生物传感器测量的动态细胞外谷氨酸的反应，以实时的mPFC中的压力，并发现在mPFC中的谷氨酸动力学显着改变慢性HPA功能障碍。总之，这些发现支持了慢性轴功能障碍改变已知调节情绪行为的区域中的神经元信号传导的假设，提供了更多的证据将功能障碍和压力脆弱性联系起来。
It is now well-established that stress elicits brain- and body-wide changes in physiology and has significant impacts on many aspects of health. The hypothalamic-pituitary-adrenal (HPA) axis is the major neuroendocrine system mediating the integrated response to stress. Appropriate engagement and termination of HPA activity enhances survival and optimizes physiological and behavioral responses to stress, while dysfunction of this system is linked to negative health outcomes such as depression, anxiety, and post-traumatic stress disorder. Glutamate signaling plays a large role in the transmission of stress-related information throughout the brain. Furthermore, aberrant glutamate signaling has negative consequences for neural plasticity and synaptic function and is linked to stress-related pathology. However, the connection between HPA dysfunction and glutamate signaling is not fully understood. We tested how HPA axis dysfunction (using low dose chronic corticosterone in the drinking water) affects glutamate homeostasis and neural responses under baseline and acute stress in male C57BL/6N mice. Using laser microdissection and transcriptomic analyses, we show that chronic disruption of the HPA axis alters the expression of genes related to glutamate signaling in the medial prefrontal cortex (mPFC), hippocampus, and amygdala. While neural responses to stress (as measured by FOS) in the hippocampus and amygdala were not affected in our model of HPA dysfunction, we observed an exaggerated response to stress in the mPFC. To further probe this we undertook in vivo biosensor measurements of the dynamics of extracellular glutamate responses to stress in the mPFC in real-time, and found glutamate dynamics in the mPFC were significantly altered by chronic HPA dysfunction. Together, these findings support the hypothesis that chronic axis dysfunction alters glutamatergic signaling in regions known to regulate emotional behavior, providing more evidence linking dysfunction and stress vulnerability.
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影响因子：
2.9
作者：
Chiba, T
通讯作者：
Chiba, T
影响因子：
16.2
作者：
Burda JE;Sofroniew MV
通讯作者：
Sofroniew MV
影响因子：
7.2
作者：
Luescher, Christian;Malenka, Robert C.
通讯作者：
Malenka, Robert C.
影响因子：
3
作者：
Colom-Lapetina, Jose;Li, Anna J.;Shansky, Rebecca M.
通讯作者：
Shansky, Rebecca M.
GABA 杏仁核系统的调节压力及其与神经精神疾病的相关性
影响因子：
4.3
作者：
Jie F;Yin G;Yang W;Yang M;Gao S;Lv J;Li B
通讯作者：
Li B