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

• Egile Nagusiak: Angelica Jardim Costa (Egilea), Adolfo Garcia Erustes (Egilea), Rita Sinigaglia (Egilea), Carlos Eduardo Neves Girardi (Egilea), Gustavo José da Silva Pereira (Egilea), Rodrigo Portes Ureshino (Egilea), Soraya Soubhi Smaili (Egilea)
• Formatua: Liburua
• Argitaratua: MDPI AG, 2021-01-01T00:00:00Z.
• Gaiak: article
• Sarrera elektronikoa: Connect to this object online.

Gaia

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.

Alearen deskribapena

10.3390/pharmaceutics13020135
1999-4923