Chronic mild stress augments MPTP induced neurotoxicity in a murine model of Parkinson's disease

Udaiyappan Janakiraman, Thamilarasan Manivasagam*, Arokiasamy Justin Thenmozhi, Chinnasamy Dhanalakshmi, Musthafa Mohamed Essa, Byoung Joon Song, Gilles J. Guillemin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)132-143
Number of pages12
JournalPhysiology and Behavior
Publication statusPublished - May 1 2017


  • Chronic mild stress
  • Experimental Parkinson's disease
  • Inflammation
  • Neurodegeneration
  • Oxidative stress
  • Signalling proteins

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience


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