Efeitos do pré e pós-tratamento com propionato de testosterona nas alterações motoras e neuroquímicas em ratos lesionados por 6-hidroxidopamina

• Ano de defesa: 2021
• Autor(a) principal: Bispo, José Marcos Meneses
• Orientador(a): Santos, José Ronaldo dos
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Programa de Pós-Graduação: Pós-Graduação em Ciências Fisiológicas
• Palavras-chave em Português: Doença de Parkinson; Testosterona; Hormônios; Gônadas; Hormônios esteroides gonadais
• Palavras-chave em Inglês: Parkinson's disease; Testosterone; Gonadal steroid hormones
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::FISIOLOGIA
• Link de acesso: https://ri.ufs.br/jspui/handle/riufs/14898

The aim of this study was to evaluate the action of pre- and post-treatments of testosterone propionate (PT) on motor and neurochemical changes in rats induced to the parkinsonism model induced by 6-hydroxydopamine (6-OHDA). All procedures were previously approved by the Animal Research Ethics Committee of UFS under protocol CEUA No. 2315030919. Seventy 10-12 months- old male Wistar rats, were used. In experiment I, the Animals of the OIL+6-OHDA and PT+ 6-OHDA groups were treated for 10 consecutive days before the injury by 6-OHDA with intramuscular injection of Sesame oil and 5.0 mg / kg of PT, respectively. Twenty-four hours after the 10th injection of PT or Sesame oil, the animals received a single, unilateral injection into the dorsal striatum of 6-OHDA. In experiment II, the animals were submitted to stereotactic surgery for the single and unilateral injection of 6-OHDA into the dorsal striatum. The animals from OIL+6-OHDA and PTin+6-OHDA groups, 24h after the injection of 6-OHDA, intramuscular injections of 5.0 mg/kg of PT or PT Vehicle (Sesame oil) until the end of the experiment. The animals in the PT+6-OHDA group started receiving daily intramuscular injections of 5.0 mg/kg of PT 7 days after the 6- OHDA injection and continued until the end of the experiment. Throughout both experiments the animals were submitted to the behavioral assessments: 1- cylinder test; 2-adhesive tape removal test and 3-open field test. After performing the open field test, the animals were anesthetized and killed by transcardiac perfusion and the brains were subjected to immunohistochemistry for thyroxine hydroxylase (TH), GFAP and CASPASE-3. Pretreatment with PT was not able to induce neuroprotection against the deleterious effects of 6-OHDA on the analyzed motor parameters. In the immunohistochemical analysis, PT administration exacerbated the deleterious effects of 6-OHDA reducing TH+ cells in SNpc and increasing the number of Caspase-3 + cells in SNpc. However, the initial administration of PT (24h after 6-OHDA injury) had a protective effect against 6-OHDA on the motor behavior in the c cylinder and open field tests in the PTin+6-OHDA group. The late administration of PT (seven days after the lion with 6-OHDA), exacerbated the deleterious effects of 6-OHDA in all the motor parameters analyzed. In the immunohistochemical analysis, the late administration of PT increased the staining for Caspase-3 in SNpc, in relation to the initial administration of PT we did not find any significant differences. Pre-administration of testosterone propionate in rats injured with the neurotoxin 6-OHDA was not effective in promoting neuroprotective effects in the analyzed parameters. The initial administration of PT (PTin + 6-OHDA group) had a protective effect on motor activity. However, the administration of late PT (PT + 6-OHDA group) after injury by 6-OHDA, exacerbated the deleterious effects of neurotoxin on motor and immunohistochemical parameters. These findings infer that testosterone in the nervous system has varied effects, but under an already established lesion, testosterone seems to promote deleterious effects.