ASSESSMENT OF ANTIDEPRESSANT THERAPY IN A PRECLINICAL PARKINSON’S DISEASE MODEL INCORPORATING UNPREDICTABLE CHRONIC MILD STRESS

Depressive disturbances, symptoms of prodromal stages of Parkinson’s Disease (PD), are prevalent in 40% to 50% of clinical PD cases. Adult hippocampal neurogenesis is reduced in both conditions, emerging as a common feature of both pathologies, suggesting that neurogenesis levels may affect PD progression. Since antidepressant treatment can modulate neurogenesis rates, we hypothesised that it would also protect the nigrostriatal system.
Adult male rats received a unilateral 6-hydroxydopamine injection into the brain to induce dopaminergic degeneration. A week later, a 6-week protocol of unpredictable chronic mild stress (uCMS) was initiated. In the last two weeks of uCMS exposure, the animals were treated with Ketamine, Escitalopram, and their combination. Those animals also received BrdU for five consecutive days during the treatment window. Several motor and non-motor tests were performed before and after administration. Furthermore, blood samples were collected from the tail vein to assess corticosterone levels, an indirect indicator of hypothalamic-pituitary-adrenal (HPA) axis dysregulation.
Preliminary results showed that stress exposure contributed to circadian cycle dysregulation, as evidenced by the absence of oscillations throughout the day. Regarding dopaminergic integrity, using tyrosine hydroxylase and dopamine transporter staining, we observed a clear decrease in 6-OHDA-PD animals, which was reflected in behavioural alterations between the treatment and control groups.
Altogether, these initial findings indicated that antidepressants may have promising therapeutic effects in PD, opening new perspectives to set the stage for future research leading to new therapeutic targets that can effectively address psychiatric symptoms associated with PD.