Funções sensoriais em um modelo progressivo de parkinsonismo

• Main Author: Cintra, Rachel Rocha
• Publication Date: 2015
• Format: Master thesis
• Language: por
• Source: Repositório Institucional da UFS
• Download full: https://ri.ufs.br/handle/riufs/3984
• topic: Doença de Parkinson; Reserpina; Nocicepção; Audição; Biomarcadores; Parkinson´s disease; Reserpine; Nociception; Audition; Biomarkers; CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA

Parkinson´s disease (PD) is a common neurodegenerative disorder of movement, which affects 1% of the population over 65 years and 4% to 5% of the population over 75 years. Currently, it is known that the disease is not only characterized by motor abnormalities, but also by a set of non-motor abnormalities that precede perhaps over several years, in preclinical phase of the disease. Studies in the premotor phase of PD are important for the understanding of when and where the disease begins to develop and how it evolves in the early stages. Although still incipient, some studies have pointed to the presence of sensory nociceptive and auditory disorders in PD. Using an animal model of PD that takes into account the progressive nature, allows a better understanding of the relationship between the pathophysiological aspects and non-motor abnormalities of the disease and enables the exploration of temporal manifestation of these changes. The aim of this study was to evaluate the nociceptive, motor and hearing functions of Wistar rats submitted to progressive model of parkinsonism induced by low and repeated doses of reserpine (RES). In the first stage, 19 Wistar rats were used, divided into two groups (n = 9/10 per group): G1: RES (0.1 mg / kg sc) and G2: CTR (RES vehicle). The animals were subjected daily to catalepsy test and the nociceptive von Frey electronic test and received injections every 48 hours for 20 days. The grip strength test was performed on days 9, 12, 14 and 17. In the second stage, the animals were divided into two groups (n = 10/11 per group) G1: RES (0, 1 mg / kg sc) and G2: CTR (RES vehicle). The catalepsy test was performed daily and the injections were made every 48 hours. On day 8, the animals were sedated to perform the hearing test of otoacoustic emissions by distortion product (DPOAE). On day 10, the nociceptive formalin test was performed, and 60 minutes later, each animal was anesthetized, perfused and their brains removed for subsequent immunohistochemical analysis for tyrosine hydroxylase (TH) and c-FOS. Repeated treatment with RES induced progressive motor abnormalities evidenced by catalepsy test from the 16th day. Likewise, induced changes in the nociceptive response of rats evidenced in electronic von Frey test and the formalin test, which occurred on the 10th day, i.e, before the motor changes. Muscle strength as measured by grip strength test, did not change with treatment. Changes in the auditory function were observed on the 8th day of treatment. Neurochemically on the 10th day, repeated treatment with the RES induced a decrease in the number of TH+ cells in the substantia nigra pars compacta (SNpc) and the ventral tegmental area (VTA) and not changed TH levels in the striatum. Regarding the immunostaining for c-FOS, noxious stimulation caused an increase in the number of cells c- FOS+ in the dorsal raphe nucleus (NDR), periaqueductal gray (PAG) and rostral ventromedial medulla (SVR) after repeated treatment with the RES, on the 10th day. We conclude that nociceptive changes precede motor changes, while the strength remains unchanged in the progressive model of parkinsonism induced by low and repeated doses of RES, reinforcing the idea that pain is one of the early signs of PD. In addition, animals with parkinsonism were more susceptible to hearing loss due to exposure to environmental noise, suggesting a possible link between the DP and the predisposition to hearing loss, including the premotor phase of the disease.