Repeated balance exercise promotes cholinergic neuroprotection of the pedunculopontine nucleus in a progressive model of Parkinson's disease

Abstract

Vestibular rehabilitation (VR) is a therapeutic approach that minimizes the impacts of balance alterations by enhancing the central vestibular compensation mechanism. The present study investigates the effect of repeated balance exercises on the central vestibular compensation mechanism in a reserpine-induced progressive model of parkinsonism in aged rats. Male Wistar rats were assigned to three cohort experiments: Exp 1: repeated balance exercises (narrow beam test) – performed every 48 h during 20 days; Exp 2: balance exercises performed on the 0^th and 8^th days; Exp 3: balance exercises performed only on the 0^th and 20^th days. For each experiment, the animals were divided into two groups (n = 7 per group): CTL (vehicle) and RES (reserpine 0.1 mg/kg). The animals received 4 (exp. 2) or 10 (exp 1 and 3) s.c. injections (0.1 mg/kg), one every 48 h. The cohorts were evaluated using catalepsy and open field tests (0^th, 8^th and 20^th days). After completion of behavioral tests, the brains were analyzed for immunohistochemistry for tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT). The RES group presented motor deficits in the catalepsy and open field tests on day 20, but not on day 8. There was no decrease in the number of TH neurons and terminals in the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA) and dorsal striatum (DS) for animals from Exp. 2. However, a decrease was observed in the SNpc, VTA and striatum of animals from Exp 1 and Exp 3. In the balance beam test, the animals in the RES group showed a longer crossing time from day 8 to day 14 (Exp 1), on the 8^th day (Exp 2) and on the 20^th day (Exp. 3). This finding was correlated with a decrease in the number of ChAT immunoreactive cells in the pedunculopontine tegmental nucleus (PPN) for the animals that performed the dynamic balance test only once (Exp. 2 and 3), but no reduction was observed in the animals that performed the test repeatedly (Epx. 1). Thus, it was possible to verify that repeated exposure of the animals to balance assessment tasks potentiated the performance of the central vestibular compensation mechanism in the animal model of parkinsonism.