Kang Ju-Bin, Park Dong-Ju, Son Hyun-Kyoung, Koh Phil-Ok
Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, 501 Jinju-daero, Jinju, 52828 South Korea.
Lab Anim Res. 2020 Sep 18;36:34. doi: 10.1186/s42826-020-00064-y. eCollection 2020.
Glutamate induces neurotoxicity during brain development, causing nerve damage. Protein phosphatase 2A (PP2A) is a type of serine/threonine phosphatase that regulates various biological functions. Among the PP2A subunit types, subunit B is abundant in brain tissue and plays an essential role in the nervous system. This study investigated changes in PP2A subunit B expression through glutamate exposure in the cerebral cortex of newborn rats. Sprague-Dawley rat pups (7 days after birth) were injected intraperitoneally with vehicle or glutamate (10 mg/kg). After 4 h of drug treatment, the brain tissue was isolated and fixed for morphological study. In addition, the cerebral cortex was collected for RNA and protein works. We observed severe histopathological changes including swollen neuron and atrophied dendrite in the glutamate exposed cerebral cortex. Glutamate exposure leads to a decrease in PP2A subunit B. Reverse-transcription PCR and Western blot analyses confirmed that glutamate induces a decrease of PP2A subunit B in the cerebral cortex of newborn rats. Moreover, immunohistochemical study showed a decrease in PP2A subunit B positive cells. The reduction of PP2A subunit B expression is considered an indicator of neurodegenerative damage. These results suggest that glutamate exposure causes neuronal damage in the cerebral cortex of new born rats through a decrease in PP2A subunit B.
谷氨酸在大脑发育过程中会诱发神经毒性，导致神经损伤。蛋白磷酸酶2A（PP2A）是一种调节多种生物学功能的丝氨酸/苏氨酸磷酸酶。在PP2A亚基类型中，B亚基在脑组织中含量丰富，在神经系统中起重要作用。本研究通过新生大鼠大脑皮层暴露于谷氨酸来研究PP2A亚基B表达的变化。将Sprague-Dawley幼鼠（出生后7天）腹腔注射溶剂或谷氨酸（10mg/kg）。药物处理4小时后，分离脑组织并固定用于形态学研究。此外，收集大脑皮层用于RNA和蛋白质研究。我们观察到在暴露于谷氨酸的大脑皮层中出现严重的组织病理学变化，包括神经元肿胀和树突萎缩。谷氨酸暴露导致PP2A亚基B减少。逆转录PCR和蛋白质印迹分析证实，谷氨酸诱导新生大鼠大脑皮层中PP2A亚基B减少。此外，免疫组织化学研究显示PP2A亚基B阳性细胞减少。PP2A亚基B表达的降低被认为是神经退行性损伤的一个指标。这些结果表明，谷氨酸暴露通过降低PP2A亚基B导致新生大鼠大脑皮层神经元损伤。
