School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China; State Key Laboratory of Medical Neurobiology & Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
State Key Laboratory of Medical Neurobiology & Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China; Shanghai Research Center for Model Organisms, Pudong, Shanghai, 201203, China.
Neurochem Int. 2018 Sep;118:195-204. doi: 10.1016/j.neuint.2018.06.010. Epub 2018 Jun 28.
Regulated endocrine-specific protein, 18 kDa (RESP18) was first cloned in 1994. Its function in the brain especially in neurodegenerative diseases remains unclear. In this study, RESP18 knockout (KO) and littermate wild-type (WT) mice were comprehensively analyzed. The dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was applied to generate subchronic Parkinson's disease model. We found that KO mice displayed a reduction in locomotor activity and motor coordination under physiological conditions. Five and six days after MPTP administration, the behavioral impairments were detected in MPTP-treated WT mice, whereas such impairments were not detected in MPTP-treated KO mice. The depletion of tyrosine hydroxylase-positive nerve fibers in the striatum was similar between MPTP-treated KO mice and WT littermates. Furthermore, the striatal level of α-synuclein protein was increased by treatment with MPTP in WT mice, but not in KO mice. The loss of dopaminergic neurons was markedly alleviated, and the activation of glial cells was inhibited in the substantia nigra of KO mice challenged with MPTP. These results suggested that RESP18 deficiency might protect dopaminergic neurons against MPTP toxicity.
调控性内分泌特定蛋白 18kDa（RESP18）于 1994 年首次被克隆。其在大脑中的功能，特别是在神经退行性疾病中的功能仍不清楚。在这项研究中，我们对 RESP18 敲除（KO）和同窝野生型（WT）小鼠进行了全面分析。应用多巴胺能毒素 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）来生成亚慢性帕金森病模型。我们发现 KO 小鼠在生理条件下表现出运动活性和运动协调能力降低。在 MPTP 处理后的第 5 天和第 6 天，WT 小鼠出现行为障碍，而在 MPTP 处理后的 KO 小鼠中未检测到这种障碍。纹状体中酪氨酸羟化酶阳性神经纤维的耗竭在 MPTP 处理的 KO 小鼠和 WT 同窝仔之间相似。此外，MPTP 处理增加了 WT 小鼠纹状体中α-突触核蛋白的水平，但在 KO 小鼠中没有增加。在 MPTP 挑战的 KO 小鼠中，黑质中的多巴胺能神经元丢失明显减轻，胶质细胞的激活受到抑制。这些结果表明，RESP18 缺失可能会保护多巴胺能神经元免受 MPTP 毒性的侵害。
