Lack of Autophagy Induction by Lithium Decreases Neuroprotective Effects in the Striatum of Aged Rats

Autor(es)

Costa, Angelica Jardim ^[1] ; Erustes, Adolfo Garcia ^[1] ; Sinigaglia, Rita ^[2] ; Neves Girardi, Carlos Eduardo ^[3] ; da Silva Pereira, Gustavo Jose ^[1] ; Ureshino, Rodrigo Portes ^{[4, 5]} ; Smaili, Soraya Soubhi ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Pharmacol, BR-04044020 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Electron Microscopy Ctr, BR-04023060 Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Psychobiol, BR-04023062 Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo, Dept Biol Sci, BR-09913030 Diadema, SP - Brazil

^[5] Univ Fed Sao Paulo, Lab Mol & Translat Endocrinol, Escola Paulista Med, BR-04039032 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICS; v. 13, n. 2 FEB 2021.
• Citações Web of Science: 0

Resumo

The pharmacological modulation of autophagy is considered a promising neuroprotective strategy. While it has been postulated that lithium regulates this cellular process, the age-related effects have not been fully elucidated. Here, we evaluated lithium-mediated neuroprotective effects in young and aged striatum. After determining the optimal experimental conditions for inducing autophagy in loco with lithium carbonate (Li2CO3), we measured cell viability, reactive oxygen species (ROS) generation and oxygen consumption with rat brain striatal slices from young and aged animals. In the young striatum, Li2CO3 increased tissue viability and decreased ROS generation. These positive effects were accompanied by enhanced levels of LC3-II, LAMP 1, Ambra 1 and Beclin-1 expression. In the aged striatum, Li2CO3 reduced the autophagic flux and increased the basal oxygen consumption rate. Ultrastructural changes in the striatum of aged rats that consumed Li2CO3 for 30 days included electrondense mitochondria with disarranged cristae and reduced normal mitochondria and lysosomes area. Our data show that the striatum from younger animals benefits from lithium-mediated neuroprotection, while the striatum of older rats does not. These findings should be considered when developing neuroprotective strategies involving the induction of autophagy in aging. (AU)

• Processo FAPESP: 17/10863-7 - Estudo da lipofagia mediada pelos receptores two-pore channels
• Beneficiário: Gustavo José da Silva Pereira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/08273-3 - Estudo da autofagia e neuroproteção no envelhecimento e em modelo farmacológico da Doença de Parkinson
• Beneficiário: Rodrigo Portes Ureshino
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/20796-2 - Estudo da autofagia mediada pelos receptores de estrógeno para combater a toxicidade da proteína tau em modelos celular e animal de zebrafish
• Beneficiário: Rodrigo Portes Ureshino
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 13/20073-2 - Estudo da autofagia no processo de proteção celular de ratas senescentes
• Beneficiário: Soraya Soubhi Smaili
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/20976-2 - Desenvolvimento, caracterização e estudos da autofagia e apoptose em modelo celular de Doença de Parkinson
• Beneficiário: Adolfo Garcia Erustes
• Modalidade de apoio: Bolsas no Brasil - Doutorado