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

Udaiyappan Janakiraman, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Rajamani Barathidasan, Chidambaram SaravanaBabu, Gilles J. Guillemin, Mohammed A S Khan

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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 in1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt.) with probenecid (250 mg/kg, s.c.) (MPTP/p) induced micemodel 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 theMPTP/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.

Original languageEnglish
Article number871
JournalPLoS One
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

Fingerprint

Probenecid
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
neurotoxicity
Parkinson disease
dopamine
Parkinson Disease
Brain
serotonin
transporters
tyrosine 3-monooxygenase
Serotonin
brain
Synucleins
Vesicular Monoamine Transport Proteins
mice
signs and symptoms (animals and humans)
Dopamine
monoamines
Dopamine Plasma Membrane Transport Proteins
Tyrosine 3-Monooxygenase

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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. / Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin; Essa, Musthafa Mohamed; Barathidasan, Rajamani; SaravanaBabu, Chidambaram; Guillemin, Gilles J.; Khan, Mohammed A S.

In: PLoS One, Vol. 11, No. 1, 871, 01.01.2016.

Research output: Contribution to journalArticle

Janakiraman, Udaiyappan ; Manivasagam, Thamilarasan ; Thenmozhi, Arokiasamy Justin ; Essa, Musthafa Mohamed ; Barathidasan, Rajamani ; SaravanaBabu, Chidambaram ; Guillemin, Gilles J. ; Khan, Mohammed A S. / 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. In: PLoS One. 2016 ; Vol. 11, No. 1.
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