Mecanismo de compensação vestibular nas alterações do equilíbrio em um modelo progressivo de parkinsonismo induzido por reserpina

Abstract

Balance alterations in Parkinson's disease (PD) have an unsatisfactory response to dopaminergic drugs used in the treatment of motor symptoms, leading to the involvement of additional neurotransmitters in the imbalance, such as the cholinergic system of the pedunculopontine nucleus (PPN). Due to the complexity of drug therapy for imbalance in PD, the present study investigated the role of the vestibular compensation mechanism in balance alterations in a reserpineinduced progressive model of parkinsonism. In experiment 1, 28 animals were randomly divided into 2 groups: control (animals treated with the vehicle – CTR) and reserpine (RES) (animals treated with 0.1 mg/kg RES), n = 14 per group. Behavioral assessments consisted of a catalepsy test (every 48h); an open field test (48h after the 2nd, 4th and 10th injections), and a balance beam test (performed on day 0 and 48h after the 4th and 10th injections). In experiment 2, 42 animals were randomly divided into 3 groups: CTR, RES, and total control (CTRt – animals treated with vehicle and not submitted to equilibrium tests), n = 14 per group. Behavioral assessments consisted of a catalepsy test, and a balance beam test (static balance and dynamic balance), all performed on day 0 and 48h after the 4th and 10th injections. An external observer randomly selected half of the animals in each group (n = 7) of both experiments to be perfused 48h after the 4th injection. The remaining animals (n = 7 per group) were perfused 48h after the 10th injection. In experiment 1, animals were submitted to immunohistochemical analysis for choline acetyltransferase (ChAT) in the pedunculopontine nucleus (PPN). In experiment 1, the RES group spent more time on the bar in the catalepsy test, from day 12 (p = 0.03) until the end of treatment – day 20 (p < 0.01) when compared with the CTR group. In the general activity of the open field test, assessed on day 20, the RES group showed a decrease in the total distance traveled (p = 0.04), mean speed (p = 0.04), and the number of rearing events (p < 0.01) when compared to the CTR group. In the balance beam test, the RES group had a longer crossing time on day 8 (p < 0.01) and on day 20 (p < 0.01) when compared to the CTR group. In PPN, there was a decrease in ChAT+ cells in the RES group that received 4 (p < 0.01) and 10 injections of reserpine (p < 0.01). In experiment 2, the RES group spent more time on the bar in the catalepsy test on day 20 (p < 0.1) when compared to the CTR group. In the static balance beam, the RES group had a shorter time on the beam on day 20 (p < 0.1), and a lower score on day 8 (p = 0.01) and on day 20 (p < 0.1) when compared to the CTR group. The RES group showed a longer crossing time on day 8 (p < 0.01) and day 20 (p < 0.01) when compared to CTR. In the present study, repeated administration of low doses (0.1 mg/kg) of reserpine was able to cause behavioral changes in balance from the initial stages. These changes were accompanied by a decreased number of immunoreactive cells for ChAT in the PPN. It was also possible to verify that the repeated xi exercises potentiated the performance of the central vestibular compensation mechanism.