title: Influences of Chronic Mild Stress Exposure on Motor, Non-Motor Impairments and Neurochemical Variables in Specific Brain Areas of MPTP/Probenecid Induced Neurotoxicity in Mice.
abstract: Parkinson's disease (PD) is regarded as a movement disorder mainly affecting the elderly population and occurs due to progressive loss of dopaminergic (DAergic) neurons in nigrostriatal pathway. Patients suffer from non-motor symptoms (NMS) such as depression, anxiety, fatigue and sleep disorders, which are not well focussed in PD research. Depression in PD is a predominant /complex symptom and its pathology lies exterior to the nigrostriatal system. The main aim of this study is to explore the causative or progressive effect of chronic mild stress (CMS), a paradigm developed as an animal model of depression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt.) with probenecid (250 mg/kg, s.c.) (MPTP/p) induced mice model of PD. After ten i.p. injections (once in 3.5 days for 5 weeks) of MPTP/p or exposure to CMS for 4 weeks, the behavioural (motor and non-motor) impairments, levels and expressions of dopamine (DA), serotonin (5-HT), DAergic markers such as tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporters-2 (VMAT 2) and α-synuclein in nigrostriatal (striatum (ST) and substantia nigra (SN)) and extra-nigrostriatal (hippocampus, cortex and cerebellum) tissues were analysed. Significantly decreased DA and 5-HT levels, TH, DAT and VMAT 2 expressions and increased motor deficits, anhedonia-like behaviour and α-synuclein expression were found in MPTP/p treated mice. Pre and/or post exposure of CMS to MPTP/p mice further enhanced the MPTP/p induced DA and 5-HT depletion, behaviour abnormalities and protein expressions. Our results could strongly confirm that the exposure of stress after MPTP/p injections worsens the symptoms and neurochemicals status of PD.
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.
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 Justin
authors.initials: AJ
authors.lastname: Thenmozhi
authors.affiliation: Department of Food Science and Nutrition, CAMS, 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: Centre for Toxicology and Developmental Research, Sri Ramachandra University, Porur, Chennai-600 116, Tamilnadu, India.
authors.forename: Rajamani
authors.initials: R
authors.lastname: Barathidasan
authors.affiliation: Centre for Toxicology and Developmental Research, Sri Ramachandra University, Porur, Chennai-600 116, Tamilnadu, India.
authors.forename: Chidambaram
authors.initials: C
authors.lastname: SaravanaBabu
authors.affiliation: Neuropharmacology group, Faculty of Medicine and Health Sciences, Deb Bailey MND Research Laboratory, Macquarie University, NSW, 2109, Australia.
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.affiliation: Harvard Medical School, Massachusetts General Hospital, Shriners Hospital for Children, Boston, Massachusetts, 02114, United States of America.
authors.forename: Mohammed A S
authors.initials: MA
authors.lastname: Khan
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D008124:Locomotion; D020267:MPTP Poisoning / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011339:Probenecid / Q000633:toxicity; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; D051844:alpha-Synuclein; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D011339:Probenecid; D004298:Dopamine