title: Aging-related 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurochemial and behavioral deficits and redox dysfunction: improvement by AK-7.
abstract: Aging is a prominent risk factor for the occurrence and progression of Parkinson disease (PD). Aging animals are more significant for PD research than young ones. It is promising to develop effective treatments for PD through modulation of aging-related molecules. Sirtuin 2 (SIRT2), a strong deacetylase highly expressed in the brain, has been implicated in the aging process. In our present study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 12mg/kg once daily) was observed to bring about significant behavioral deficits and striatal dopamine depletion in aging male and female mice, while it did not do so in young animals. MPTP did not cause significant reduction in striatal 5-hydroxytryptamine content in aging male and female mice. Furthermore, we observed that MPTP treatment resulted in significant reduction in GSH content and significant increase in MDA content and SIRT2 expression in the substantia nigra (SN) of aging mice, while it did not do so in young animals. Importantly, we observed that AK-7 (a selective SIRT2 inhibitor) significantly improved behavior abnormality and neurochemical deficits in aging male and female mice treated with MPTP. Significant increase in GSH content and significant decrease in MDA content were also observed in the SN of aging male and female mice co-treated with MPTP and AK-7 compared with the MPTP-treated animals. Our results indicated that MPTP induce aging-related neurochemical and behavioural deficits and dysfunction of redox network in male and female mice and AK-7 may be neuroprotective in PD through modulating redox network.
authors.affiliation: Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui 230009, China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Shanghai Laboratory Animal Center, Chinese Academy of Sciences, Shanghai 201615, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address: ychwjs2004@163.com.
authors.forename: Xijin
authors.initials: X
authors.lastname: Wang
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000375:Aging / Q000187:drug effects*; D000818:Animals; D000067290:Behavior Rating Scale; D001549:Benzamides / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: C000603971:3-(1-azepanylsulfonyl)-N-(3-bromphenyl)benzamide; D001549:Benzamides; D018696:Neuroprotective Agents; D013449:Sulfonamides; D008315:Malondialdehyde; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C418743:Sirt2 protein, mouse; D056565:Sirtuin 2; D005978:Glutathione
keywords: AK-7; Aging; Behavior; GSH; MDA; Neurotransmitter