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.
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Parkinson's disease patients have lower concentrations of BDNF mRNA and protein in the substantia nigra pars compacta than healthy controls.
“PD patients have lower concentrations of BDNF mRNA and protein in the substantia nigra pars compacta than healthy controls [164, 165].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [164]
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- Authors
- Janakiraman, U., Manivasagam, T., Justin Thenmozhi, A., Dhanalakshmi, C., Essa, M. M., Song, B.-J., & Guillemin, G. J.
- Affiliations
- Annamalai University (IN)
- Sultan Qaboos University (OM)
- National Institutes of Health (US)
- Macquarie University (AU)
- Corresponding author
- Manivasagam, Thamilarasan
- ORCID
- Venue
- Physiology & Behavior
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 173
- Pages
- 132-143
- ISSN
- 0031-9384 (ISSN-L)
- OpenAlex
- W2587026981
- Cited by
- 36
- References
- 79
- Citations by year
- 2026: 3 · 2025: 5 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 8 · 2019: 5 · 2018: 7 · 2017: 1
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiology & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Biotechnology, Government of West Bengal
- National Health and Medical Research Council (APP1128849)
- Australian Research Council (ARC - FT120100397)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- chronic mild stress, Parkinson's disease, MPTP-induced neurotoxicity, depression, non-motor symptoms, oxidative stress, neuroinflammation, brain-derived neurotrophic factor, Akt signaling, CREB, serotonin transporter, anxiety, motor impairment, nigrostriatal pathway, stress timing
- MeSH terms
- Adjuvants, Pharmaceutic, Animals, Body Weight, Calcium-Binding Proteins, Catalase, Disease Models, Animal, Exploratory Behavior, Glial Fibrillary Acidic Protein, Male, Mice, Inbred C57BL, Microfilament Proteins, Probenecid, Stress, Psychological, Superoxide Dismutase, Thiobarbiturates, Signal Transduction, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Thiobarbituric Acid Reactive Substances, Maze Learning, Brain-Derived Neurotrophic Factor, Parkinsonian Disorders, Mice, Muscle Strength
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