Avaliação da modulação da Na+ , K+ -ATPase em doenças neurológicas: revisão sistemática, metanálise e evidências in vivo

• Ano de defesa: 2024
• Autor(a) principal: Mello, Fernanda Kulinski
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; Farmacologia; UFSM; Programa de Pós-Graduação em Farmacologia; Centro de Ciências da Saúde
• Palavras-chave em Português: Na+ , K+ - ATPase; Doenças neurológicas; Epilepsia; DRRSAb; Epilepsy; Neurologic diseases; CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
• Link de acesso: http://repositorio.ufsm.br/handle/1/33224

More than a third of the world's population suffers from a neurological disease, unfortunately, most of these diseases are not effectively treated and cannot be cured. Among them is epilepsy, which affects around 50 million people and the pharmacological treatment is ineffective for 30% of patients. The enzyme Na+ , K+ -ATPase is a key regulator of brain excitability and its inhibition is related to several diseases and is potentially a common point between them. The aim of this study was to evaluate the effect of a positive modulator of this enzyme, administered intranasally, in an animal model of pilocarpine-induced SE and to determine the degree of inhibition of the Na+ , K+ -ATPase enzyme in animal models of neurological diseases using a systematic review. In the in vivo experiment, 32 male Wistar rats underwent surgery to implant electrodes and after 72 hours they underwent the pilocarpine or control protocol and subsequently received DRRSAb or vehicle intranasally. The animals were divided into four groups; group 1 (vehicle control) NaCl 0.9% i.p. + NaCl 0.9% i.n. (5µL/nostril); group 2 (control-DRRSAb) NaCl 0.9% i.p. + DRRSAb i.n. (2µg/nostril); group 3 (SE+vehicle) pilocarpine 300mg/kg i.p. + NaCl 0.9% i.n. (5µL/nostril); and group 4 (SE+DRRSAb) pilocarpine 300mg/kg i.p. + DRRSAb i.n. (2µg/nostril) After 1 hour of establishing the SE, the animals received treatment intranasally and electroencephalographic changes were recorded for another hour. Additionally, the animals were evaluated with behavioral tests of neuroscore, pick up, open field, elevated plus maze and object recognition 7 days after SE induction. The review was carried out using the PubMed, SCOPUS and Web of Science platforms and the protocol is available on the OSF platform. A total of 29 articles were included, enzyme inhibition data were collected, and meta-analysis was performed and expressed as percentage of control. In the in vivo study, the activating antibody increased spectral density in the EEG and caused an increase in theta, beta and gamma rhythms immediately after SE. When evaluated one week after SE, animals treated with the antibody had better performance in the tests. pick up and memory, demonstrating that a single administration of the antibody intranasally is capable of protecting against cognitive and neuromotor impairments one week after SE. The results of the systematic review show that the enzyme is reduced in all diseases evaluated, the activity was on average 37% less when compared to the respective controls. Based on these results, it is possible to conclude that the Na+ , K+ -ATPase is a key point in the neurological diseases studied and its downregulation may be related to the pathological process of several neurological diseases, and thus, the enzyme activating antibody, DRRSAb, may be a promising approach for the treatment of neurological diseases.