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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)132-143
Number of pages12
JournalPhysiology and Behavior
Volume173
DOIs
Publication statusPublished - May 1 2017

Fingerprint

Probenecid
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Parkinson Disease
Oxidative Stress
Brain-Derived Neurotrophic Factor
Depression
Inflammation
Anxiety
Serotonin Plasma Membrane Transport Proteins
Parkinsonian Disorders
Heat-Shock Proteins
Parkinson's Disease
Inbred C57BL Mouse
4-phenyl-1,2,3,6-tetrahydropyridine
Mouse

Keywords

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

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Philosophy
  • Behavioral Neuroscience

Cite this

Janakiraman, U., Manivasagam, T., Justin Thenmozhi, A., Dhanalakshmi, C., Essa, M. M., Song, B. J., & Guillemin, G. J. (2017). Chronic mild stress augments MPTP induced neurotoxicity in a murine model of Parkinson's disease. Physiology and Behavior, 173, 132-143. https://doi.org/10.1016/j.physbeh.2017.01.046

Chronic mild stress augments MPTP induced neurotoxicity in a murine model of Parkinson's disease. / Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Dhanalakshmi, Chinnasamy; Essa, Musthafa Mohamed; Song, Byoung Joon; Guillemin, Gilles J.

In: Physiology and Behavior, Vol. 173, 01.05.2017, p. 132-143.

Research output: Contribution to journalArticle

Janakiraman, U, Manivasagam, T, Justin Thenmozhi, A, Dhanalakshmi, C, Essa, MM, Song, BJ & Guillemin, GJ 2017, 'Chronic mild stress augments MPTP induced neurotoxicity in a murine model of Parkinson's disease', Physiology and Behavior, vol. 173, pp. 132-143. https://doi.org/10.1016/j.physbeh.2017.01.046
Janakiraman, Udaiyappan ; Manivasagam, Thamilarasan ; Justin Thenmozhi, Arokiasamy ; Dhanalakshmi, Chinnasamy ; Essa, Musthafa Mohamed ; Song, Byoung Joon ; Guillemin, Gilles J. / Chronic mild stress augments MPTP induced neurotoxicity in a murine model of Parkinson's disease. In: Physiology and Behavior. 2017 ; Vol. 173. pp. 132-143.
@article{09cea30b0e0d41b8afeb1732d782b012,
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.",
keywords = "Chronic mild stress, Experimental Parkinson's disease, Inflammation, Neurodegeneration, Oxidative stress, Signalling proteins",
author = "Udaiyappan Janakiraman and Thamilarasan Manivasagam and {Justin Thenmozhi}, Arokiasamy and Chinnasamy Dhanalakshmi and Essa, {Musthafa Mohamed} and Song, {Byoung Joon} and Guillemin, {Gilles J.}",
year = "2017",
month = "5",
day = "1",
doi = "10.1016/j.physbeh.2017.01.046",
language = "English",
volume = "173",
pages = "132--143",
journal = "Physiology and Behavior",
issn = "0031-9384",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Chronic mild stress augments MPTP induced neurotoxicity in a murine model of Parkinson's disease

AU - Janakiraman, Udaiyappan

AU - Manivasagam, Thamilarasan

AU - Justin Thenmozhi, Arokiasamy

AU - Dhanalakshmi, Chinnasamy

AU - Essa, Musthafa Mohamed

AU - Song, Byoung Joon

AU - Guillemin, Gilles J.

PY - 2017/5/1

Y1 - 2017/5/1

N2 - 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.

AB - 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.

KW - Chronic mild stress

KW - Experimental Parkinson's disease

KW - Inflammation

KW - Neurodegeneration

KW - Oxidative stress

KW - Signalling proteins

UR - http://www.scopus.com/inward/record.url?scp=85012072415&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85012072415&partnerID=8YFLogxK

U2 - 10.1016/j.physbeh.2017.01.046

DO - 10.1016/j.physbeh.2017.01.046

M3 - Article

C2 - 28185878

AN - SCOPUS:85012072415

VL - 173

SP - 132

EP - 143

JO - Physiology and Behavior

JF - Physiology and Behavior

SN - 0031-9384

ER -