title: Chronic mild stress augments MPTP induced neurotoxicity in a murine model of Parkinson's disease.
abstract: Depression is frequently encountered during Parkinson's disease (PD) as a non-motor feature, which has been reported to cause and exaggerate motor deficits and neurodegenerative events in experimental PD models. We studied the effect of chronic mild stress (CMS) (pre, post and pre & post) exposure mediated depression on motor and non-motor symptoms, oxidative stress, inflammation and brain derived neurotrophic factor (BDNF) levels and its related signalling molecules against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) induced neurotoxicity in mice. CMS and MPTP/p-coexposed C57BL/6 mice exhibited low neuromuscular strength and stride length with enhanced oxidative stress and inflammation as compared to CMS or MPTP/p alone exposed mice. Coexposure diminished the levels of BDNF and expressions of p-TrkB, p-ERK/ERK, p-AKT/AKT and p-CREB in nigrostriatal regions as compared to those of the alone exposure. CMS alone exposed mice showed more anxiety related behaviour with diminished expression of serotonin transporter as compared to MPTP/p alone injected group. Post-stress exposure to MPTP/p mice exhibited lowest motor and reflecting higher anxiety state with greatest enhancement in inflammation and reduction in the protein expression of stress and cell signalling markers as compared to pre and pre & post stress exposed PD mice. However, pre- and pre & post CMS exposed PD animals are more vulnerable to oxidative stress as compared with post-stress experienced MPTP/p mice. CMS mediated depression exacerbates motor/non-motor symptoms in MPTP/p-PD animals by modulating oxidative stress and various signalling molecules. Our results suggested that stress induced NMS can accelerate neurodegenerative processes in the PD in a progressive or expedited manner.
authors.affiliation: Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, 608002, Tamilnadu, India.
authors.forename: Udaiyappan
authors.initials: U
authors.lastname: Janakiraman
authors.affiliation: Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, 608002, Tamilnadu, India. Electronic address: mani_pdresearchlab@rediff.com.
authors.forename: Thamilarasan
authors.initials: T
authors.lastname: Manivasagam
authors.affiliation: Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, 608002, Tamilnadu, India.
authors.forename: Arokiasamy
authors.initials: A
authors.lastname: Justin Thenmozhi
authors.affiliation: Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, 608002, Tamilnadu, India.
authors.forename: Chinnasamy
authors.initials: C
authors.lastname: Dhanalakshmi
authors.affiliation: Department of Food Science and Nutrition, Sultan Qaboos University, Muscat, Oman; Ageing and Dementia Research Group, Sultan Qaboos University, Muscat, Oman.
authors.forename: Musthafa Mohamed
authors.initials: MM
authors.lastname: Essa
authors.affiliation: NIAA, National Institute of Health, Rockville, MD, USA.
authors.forename: Byoung-Joon
authors.initials: BJ
authors.lastname: Song
authors.affiliation: Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia; Neuropharmacology Group, ASAM, Macquarie University, Sydney, NSW, Australia.
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D000277:Adjuvants, Pharmaceutic / Q000633:toxicity; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D053580:Muscle Strength / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D011339:Probenecid / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013858:Thiobarbiturates / Q000633:toxicity; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000277:Adjuvants, Pharmaceutic; C100745:Aif1 protein, rat; D019208:Brain-Derived Neurotrophic Factor; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D013858:Thiobarbiturates; D017392:Thiobarbituric Acid Reactive Substances; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002374:Catalase; D013482:Superoxide Dismutase; C029684:thiobarbituric acid; D011339:Probenecid
keywords: Chronic mild stress; Experimental Parkinson's disease; Inflammation; Neurodegeneration; Oxidative stress; Signalling proteins