From the Cytoneurobiology Unit, Department of Anatomy, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
J Neuropathol Exp Neurol. 2020 Feb 1;79(2):194-208. doi: 10.1093/jnen/nlz113.
There are reports that depression induced by frontal lobe injury (FLI) has a devastating effect on human mental health. We previously reported that fasciculation and elongation protein zeta-1 (FEZ1) was essential for astrocytic protection of dopamine neurons. Studies of glutamate-glutamine cycle in mental illness have been reported, whereas not from the perspective of astrocytes. This study was designed to investigate the roles of astrocytic FEZ1 and glutamate-glutamine cycle after FLI. A model of FLI was established by inserting a blade into the right frontal lobe of rats. Behavioral tests were used to observe the behavioral changes of FLI rats. Neuropathologic examinations, including immunohistochemistry, were conducted. Behavioral tests showed that FLI decreased exploratory activity. Western blot analysis revealed that the expression of astroglial proteins overall decreased in the initial injury stage, as well as FEZ1. Immunohistochemistry showed a shift of FEZ1 localization from neurons in sham-lesioned rats to astrocytes in FLI rats, and showed the expression profile of glutamate transporter 1 and glutamine synthetase (GS) was consistent with Western blot observation. Our results indicate that astrocytic FEZ1 and glutamate-glutamine cycle dysfunction may be involved in the pathogenesis of depression after FLI.
有报道称，额叶损伤（FLI）引起的抑郁对人类心理健康有毁灭性的影响。我们之前报道过，束丝蛋白ζ-1（FEZ1）对于星形胶质细胞保护多巴胺神经元是必需的。已有关于精神疾病中谷氨酸-谷氨酰胺循环的研究，但不是从星形胶质细胞的角度。本研究旨在探讨 FLI 后星形胶质细胞 FEZ1 和谷氨酸-谷氨酰胺循环的作用。通过将刀片插入大鼠右额叶来建立 FLI 模型。使用行为测试来观察 FLI 大鼠的行为变化。进行神经病理学检查，包括免疫组织化学。行为测试表明 FLI 降低了探索性活动。Western blot 分析显示，初始损伤阶段星形胶质细胞蛋白的总体表达以及 FEZ1 减少。免疫组织化学显示 FEZ1 的定位从假损伤大鼠的神经元转移到 FLI 大鼠的星形胶质细胞，并且谷氨酸转运蛋白 1 和谷氨酰胺合成酶（GS）的表达谱与 Western blot 观察一致。我们的结果表明，星形胶质细胞 FEZ1 和谷氨酸-谷氨酰胺循环功能障碍可能与 FLI 后抑郁的发病机制有关。
