Metformin improves depressive-like behavior in experimental Parkinson's disease by inducing autophagy in the substantia nigra and hippocampus.

Autor: Mendonça IP; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (FIOCRUZ), Recife, PE, Brazil. ingridpratamendoca@gmail.com.; Postgraduate Program in Biological Sciences (PPGCB), Federal University of Pernambuco (UFPE), Recife, Brazil. ingridpratamendoca@gmail.com., de Paiva IHR; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (FIOCRUZ), Recife, PE, Brazil.; Postgraduate Program in Biological Sciences (PPGCB), Federal University of Pernambuco (UFPE), Recife, Brazil., Duarte-Silva EP; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (FIOCRUZ), Recife, PE, Brazil.; Postgraduate Program in Biosciences and Biotechnology for Health (PPGBBS), Oswaldo Cruz Foundation (FIOCRUZ-PE)/Aggeu Magalhães Institute (IAM), Recife, PE, Brazil., de Melo MG; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (FIOCRUZ), Recife, PE, Brazil.; Postgraduate Program in Biological Sciences (PPGCB), Federal University of Pernambuco (UFPE), Recife, Brazil., da Silva RS; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (FIOCRUZ), Recife, PE, Brazil.; Postgraduate Program in Biological Sciences (PPGCB), Federal University of Pernambuco (UFPE), Recife, Brazil., do Nascimento MIX; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (FIOCRUZ), Recife, PE, Brazil., Peixoto CA; Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (FIOCRUZ), Recife, PE, Brazil. peixoto.christina@gmail.com.; National Institute of Science and Technology On Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. peixoto.christina@gmail.com.
Jazyk: angličtina
Zdroj: Inflammopharmacology [Inflammopharmacology] 2022 Oct; Vol. 30 (5), pp. 1705-1716. Date of Electronic Publication: 2022 Aug 06.
DOI: 10.1007/s10787-022-01043-6
Abstrakt: Parkinson's disease (PD) remains a disease of little known etiology. In addition to the motor symptoms, depression is present in about 40% of patients, contributing to the loss of quality of life. Recently, the involvement of the autophagy mechanism in the pathogenesis of depression has been studied, in addition to its involvement in PD as well. In this study, we tested the effects of metformin, an antidiabetic drug also with antidepressant effects, on depressive-like behavior in a rotenone-induced PD model and on the autophagy process. Mice 8-week-old male C57BL/6 were induced with rotenone for 20 consecutive days (2.5 mg/kg/day) and treated with metformin (200 mg/kg/day) from the 5th day of induction. All the animals were submitted to rotarod, sucrose preference and tail suspension tests. After euthanasia, the substantia nigra and hippocampus were removed for analysis by western blotting or fixed and analyzed by immunofluorescence. The results show that there was an impairment of autophagy in animals induced by rotenone both in nigral and extranigral regions as well as a depressive-like behavior. Metformin was able to inhibit depressive-like behavior and increase signaling pathway proteins, transcription factors and autophagosome-forming proteins, thus inducing autophagy in both the hippocampus and the substantia nigra. In conclusion, we show that metformin has an antidepressant effect in a rotenone-induced PD model, which may result, at least in part, from the induction of the autophagy process.
(© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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