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 in1-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.

Fenugreek Seed Powder Nullified Aluminium Chloride Induced Memory Loss, Biochemical Changes, Aβ Burden and Apoptosis via Regulating Akt/GSK3β Signaling Pathway

“…The pellets were re-suspended in cold buffer without sucrose and considered as the mitochondrial fraction. Supernatant was collected and centrifuged at 100,000 × g for 60 min at 4°C and the pellet obtained was then considered as cytosolic fraction [28]. Protein concentration in both the tissue fractions was analyzed by the method of Lowry et al, [29].…”

An Integrated Review of Psychological Stress in Parkinson’s Disease: Biological Mechanisms and Symptom and Health Outcomes

“…Of the 11 studies included in this review, seven examined biological mechanisms of psychological stress that contribute to pathophysiological processes and symptom outcomes in animal models of PD [55–61]. In contrast, the remaining four studies focused on biological mechanisms, symptom, and/or health outcomes of psychological stress that may modify the illness trajectory in human subjects with PD [62–65].…”

“…Seven of the studies included in this review examined biological mechanisms and symptom outcomes of psychological stress in animal models of PD [55–61]. Health outcomes of psychological stress were not examined in these studies.…”

“…Health outcomes of psychological stress were not examined in these studies. Biological mechanisms in the reviewed studies included biomarkers of dopamine production and metabolism [55, 56, 58–61], serotonin (5-HT) [55], norepinephrine [61], and/or dopaminergic neurodegeneration [57, 58]. In addition, two studies examined biological mechanisms associated with stress responses of the neuroendocrine system, specifically the effects of corticosterone administration [57] and norepinephrine levels [61] on motor symptom outcomes.…”

“…In addition, two studies examined biological mechanisms associated with stress responses of the neuroendocrine system, specifically the effects of corticosterone administration [57] and norepinephrine levels [61] on motor symptom outcomes. Of particular importance, one study [55] examined the effects of psychological stress on the expression of α -synuclein, a misfolded protein complex that is recognized as a pathological hallmark of PD. All of the animal studies included in this review examined symptom outcomes specific to the motor manifestations of PD [55–61].…”