Bali Balázs, Erdélyi Ferenc, Szabó Gábor, Kovács Krisztina J
Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, P.O. Box 67, H-1450 Budapest, Hungary.
Neurosci Lett. 2005;380(1-2):60-5. doi: 10.1016/j.neulet.2005.01.014. Epub 2005 Jan 22.
Here, we have revealed that a subset of GABAergic neurons in the mouse brain became activated during systemic stress response. Stress-induced expression of immediate early gene product c-Fos, as a marker of neuronal activation was visualized in a transgenic mouse line expressing enhanced green fluorescent protein (eGFP) under the control of the regulatory region of mouse glutamic acid decarboxylase (GAD) 65 gene. In most GABAergic regions egfp transgene expression corresponded to acknowledged distribution of GABA neurons. Ether inhalation, as a strong systemic stressor induced c-Fos expression throughout the stress-related circuit, and did not affect the distribution and expression of the eGFP-transgene. Stress provoked strong neuronal activation in the piriform cortex, midline thalamic nuclei, lateral septum (LS), bed nucleus of the stria terminalis (BNST), and in parvocellular part of the hypothalamic paraventricular nucleus (PVN) as revealed by c-Fos immunfluorescence. Cells in the LS, BNST, and AHA including the subparaventricular zone (SPVZ) displayed significant eGFP/c-Fos co-localization, revealing stress-responsive GABAergic neurons. None of the stress-activated neurons within the medial parvocellular subdivision of the PVN were GABAergic. Our present results suggest that stress-recruited GABAergic neuron populations are preferentially located in distinct limbic and hypothalamic regions and these neurons might be involved in an inhibitory mechanism that counteract the endocrine, autonomic and behavioral aspects of the stress response. Furthermore, the present GAD65-eGFP transgenic model seems to be a relevant tool to analyze inhibitory control of the central stress circuit at single cell level.
在此，我们发现小鼠大脑中的一部分γ-氨基丁酸能神经元在全身应激反应期间被激活。作为神经元激活标志物的即刻早期基因产物c-Fos的应激诱导表达，在一个在小鼠谷氨酸脱羧酶（GAD）65基因调控区控制下表达增强型绿色荧光蛋白（eGFP）的转基因小鼠品系中得以显现。在大多数γ-氨基丁酸能区域，eGFP转基因表达与公认的γ-氨基丁酸能神经元分布相对应。乙醚吸入作为一种强烈的全身应激源，在整个应激相关回路中诱导了c-Fos表达，并且不影响eGFP转基因的分布和表达。如c-Fos免疫荧光所示，应激在梨状皮质、中线丘脑核、外侧隔（LS）、终纹床核（BNST）以及下丘脑室旁核（PVN）的小细胞部引发了强烈的神经元激活。LS、BNST以及包括室旁核下区（SPVZ）在内的前下丘脑区（AHA）中的细胞显示出显著的eGFP/c-Fos共定位，揭示了应激反应性γ-氨基丁酸能神经元。PVN内侧小细胞亚区中应激激活的神经元均不是γ-氨基丁酸能的。我们目前的结果表明，应激募集的γ-氨基丁酸能神经元群体优先位于不同的边缘和下丘脑区域，并且这些神经元可能参与一种抑制机制，该机制可抵消应激反应的内分泌、自主神经和行为方面。此外，目前的GAD65-eGFP转基因模型似乎是在单细胞水平分析中枢应激回路抑制控制的一个相关工具。
