Debora M. G. Cunha

Parkinson’s disease (PD) is a multifactorial condition associated with genetic and environmental factors. In recent years, the role of chronic psychophysiological stress as a predisposing factor for PD is gaining increasing attention. Clinical and experimental evidence indicates that chronic stress exerts adverse effects on the brain. Nevertheless, the potential role of chronic stress in the predisposition to PD remains poorly understood. This study aimed to investigate the effects of exposure to a chronic unpredictable mild stress (UMS) protocol on the onset of parkinsonism in Wistar rats repeatedly treated with a low dose of reserpine. Wistar rats were either exposed to UMS for 1 week or not exposed (control group). Then, the animals were repeatedly treated with a low dose of reserpine or vehicle every other day for 20 days. Behavioral motor evaluations were conducted using catalepsy and open field tests. Moreover, plasma corticosterone (CORT) levels and lipid peroxidation were evaluated. As expected, the UMS protocol increased plasma CORT levels, and reserpine treatment led to a progressive enhancement of cataleptic behavior. Animals exposed to UMS and treated with reserpine exhibited motor alteration earlier during the protocol. No differences were observed in oxidative stress between experimental and control groups, as evaluated through lipid peroxidation assay. Our results showed that chronic mild stress accelerated the onset of motor deficits in reserpine-treated animals.

Despite recent efforts to search for biomarkers for the pre-symptomatic diagnosis of Parkinson’s disease (PD), the presence of risk factors, prodromal signs, and family history still support the classification of individuals at risk for this disease. Human epidemiological studies are useful in this search but fail to provide causality. The study of well-known risk factors for PD in animal models can help elucidate mechanisms related to the disease’s etiology and contribute to future prevention or treatment approaches. This narrative review aims to discuss animal studies that investigated four of the main risk factors and/or prodromal signs related to PD: advanced age, male sex, sleep alterations, and depression. Different databases were used to search the studies, which were included based on their relevance to the topic. Although still in a reduced number, such studies are of great relevance in the search for evidence that leads to a possible early diagnosis and improvements in methods of prevention and treatment.