Niu Xue-Yuan, Huang Hou-Ju, Zhang Jin-Bao, Zhang Chan, Chen Wei-Guang, Sun Chen-You, Ding Yu-Qiang, Liao Min
Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Neuroscience. 2016 Dec 17;339:22-31. doi: 10.1016/j.neuroscience.2016.09.037. Epub 2016 Sep 28.
Parkinson's disease (PD) is a neurodegenerative disease caused by a gradual loss of midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta (SNpc) during aging. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is one of the neurotoxins used widely to induce PD-like symptoms in PD animal models, including rodents and non-human primates. It has been reported that deletion of autophagy-related gene 7 (Atg7) in the brain results in a reduction of mDA neurons in adulthood. In this study, we used tyrosine hydroxylase (TH)-Cre mice to generate conditional knockout (CKO) mice with the specific deletion of Atg7 in mDA neurons. Consistent with previous reports, adult Atg7 CKO mice contained fewer TH-positive mDA neurons compared with wild-type (WT) controls. TH-expressing neurons containing puncta-like structures with p62 and ubiquitin immunoreactivity were observed in the midbrain of Atg7 CKO mice but were not detected in control mice. However, MPTP-induced loss of mDA neurons was not observed in Atg7 CKO mice. Our results indicate that Atg7-involved autophagy is required not only for the survival of mDA neurons in the mouse brain, but also for MPTP-induced mDA neuron degeneration.
帕金森病（PD）是一种神经退行性疾病，由衰老过程中黑质致密部（SNpc）的中脑多巴胺能（mDA）神经元逐渐丧失所致。1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）是一种广泛用于在包括啮齿动物和非人类灵长类动物在内的PD动物模型中诱导PD样症状的神经毒素。据报道，大脑中自噬相关基因7（Atg7）的缺失会导致成年期mDA神经元数量减少。在本研究中，我们使用酪氨酸羟化酶（TH）-Cre小鼠来生成mDA神经元中Atg7特异性缺失的条件性敲除（CKO）小鼠。与先前的报道一致，成年Atg7 CKO小鼠与野生型（WT）对照相比，TH阳性mDA神经元数量更少。在Atg7 CKO小鼠的中脑中观察到含有p62和泛素免疫反应性点状结构的TH表达神经元，但在对照小鼠中未检测到。然而，在Atg7 CKO小鼠中未观察到MPTP诱导的mDA神经元丧失。我们的结果表明，Atg7参与的自噬不仅是小鼠大脑中mDA神经元存活所必需的，也是MPTP诱导的mDA神经元变性所必需的。
