Deletion of autophagy-related gene 7 in dopaminergic neurons prevents their loss induced by MPTP.
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.
Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Xue-Yuan
XY
Niu
Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Hou-Ju
HJ
Huang
Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Jin-Bao
JB
Zhang
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Chan
C
Zhang
Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Wei-Guang
WG
Chen
Department of Human Anatomy, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Chen-You
CY
Sun
Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Department of Anatomy and Neurobiology, and Collaborative Innovation Center for Brain Science, Tongji University School of Medicine, Shanghai 200092, China. Electronic address: dingyuqiang@vip.163.com.
Yu-Qiang
YQ
Ding
Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: liaomin70@126.com.
Min
M
Liao
D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D000071193:Autophagy-Related Protein 7 / Q000172:deficiency* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D005684:Gait / Q000187:drug effects / Q000502:physiology; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000066829:Neuroprotection / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
C502661:Atg7 protein, mouse; D025801:Ubiquitin; D014446:Tyrosine 3-Monooxygenase; D000071193:Autophagy-Related Protein 7
Atg7; MPTP; Parkinson’s disease; autophagy