Deletion of autophagy-related gene 7 in dopaminergic neurons prevents their loss induced by MPTP. (17th December 2016)

• Record Type: Journal Article
• Authors: Niu, Xue-Yuan; Huang, Hou-Ju; Zhang, Jin-Bao; Zhang, Chan; Chen, Wei-Guang; Sun, Chen-You; Ding, Yu-Qiang; Liao, Min
• Is Part Of: Neuroscience. Volume 339(2016)
• Page Start: 22
• Page End: 31
• Publication Date: 2016-12-17
• Subjects: Atg7 autophagy-related gene 7 -- CKO conditional knockout -- mDA midbrain dopaminergic -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- OD optical density -- PBS phosphate-buffered saline -- PD Parkinson's disease -- SNpc substantia nigra pars compacta -- TH tyrosine hydroxylase -- WT wild-type; Atg7 -- MPTP -- autophagy -- Parkinson's disease; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.09.037
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Generation of Atg7 CKO mice with specific deletion of Atg7 in mDA neurons. Adult Atg7 CKO mice contain fewer TH-positive mDA neurons compared with age-matched controls. MPTP-induced loss of mDA neurons is not present in Atg7 CKO mice. Abstract: 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.