title: Cyclosporine A and MnTMPyP Alleviate α-Synuclein Expression and Aggregation in Cypermethrin-Induced Parkinsonism.
abstract: Cypermethrin induces the mitochondrial dysfunction and oxidative damage to the nigrostriatal dopaminergic neurons leading to Parkinsonism in rats. Despite α-synuclein aggregation is reported to be critical in Parkinson's disease, its role and alliance with the mitochondrial dysfunction and oxidative damage leading to cypermethrin-induced Parkinsonism have not yet been deciphered. The present study aimed to examine the effect of cypermethrin on the expression and aggregation of α-synuclein and its subsequent connection with oxidative damage and mitochondrial dysfunction leading to the nigrostriatal dopaminergic neurodegeneration in the presence or absence of a mitochondrial membrane transition pore opening inhibitor, cyclosporine A and a superoxide dismutase/catalase mimetic, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP). The expression of α-synuclein, 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE)-modified proteins, mitochondrial dysfunction-dependent apoptotic proteins, nitrite content, lipid peroxidation (LPO) and number of tyrosine hydroxylase (TH)-positive neurons were estimated in the substantia nigra and dopamine content in the striatum of control and treated rats employing standard procedures. Cypermethrin augmented the expression of α-synuclein, 3-NT, 4-HNE-modified proteins, caspase-3, mitochondrial Bax and cytosolic cytochrome-c along with nitrite and LPO and reduced the expression of cytosolic Bax, mitochondrial cytochrome-c, dopamine and number of TH-positive neurons. Cyclosporine A or MnTMPyP alleviated the expression and aggregation of α-synuclein along with indicators of the mitochondrial dysfunction, oxidative damage and dopaminergic neurodegeneration. The results demonstrate that cypermethrin induces α-synuclein expression and aggregation while cyclosporine A or MnTMPyP rescues from α-synuclein over-expression and aggregation along with the mitochondrial dysfunction and oxidative damage leading to Parkinsonism in rats.
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box No. 80, Lucknow, 226001, Uttar Pradesh, India.|Academy of Scientific and Innovative Research, New Delhi, 110025, India.
authors.forename: Sonal
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box No. 80, Lucknow, 226001, Uttar Pradesh, India.
authors.forename: Anubhuti
authors.initials: A
authors.lastname: Dixit
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box No. 80, Lucknow, 226001, Uttar Pradesh, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Singh
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box No. 80, Lucknow, 226001, Uttar Pradesh, India.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Tripathi
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box No. 80, Lucknow, 226001, Uttar Pradesh, India.
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Singh
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box No. 80, Lucknow, 226001, Uttar Pradesh, India.
authors.forename: Devendra Kumar
authors.initials: DK
authors.lastname: Patel
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box No. 80, Lucknow, 226001, Uttar Pradesh, India. singhmahendrapratap@rediffmail.com.|Academy of Scientific and Innovative Research, New Delhi, 110025, India. singhmahendrapratap@rediffmail.com.
authors.forename: Mahendra Pratap
authors.initials: MP
authors.lastname: Singh
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects; D008665:Metalloporphyrins / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism; D011722:Pyrethrins / Q000494:pharmacology*; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects; D051844:alpha-Synuclein / Q000187:drug effects* / Q000378:metabolism
chemical_list: D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D011722:Pyrethrins; D051844:alpha-Synuclein; C017160:cypermethrin; D016572:Cyclosporine
keywords: Cyclosporine A; Mitochondrial dysfunction; MnTMPyP; Oxidative damage, cypermethrin-induced Parkinsonism; α-Synuclein