Abstract
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.
Highlights
There is a progressive loss of cellular homeostasis during aging, accompanied by a reduction in the progenitor cell reserve
As shown in Figure determined the concentration time required for inducing autophagy in the1a, striatal slices from young rats were treated in loco with three different concentrations young samples, as evidenced by an increase in LC3-II expression
Generation and oxygen consumption in young and aged striatum treated with lithium
Summary
There is a progressive loss of cellular homeostasis during aging, accompanied by a reduction in the progenitor cell reserve. These results were seen in many senescent cells that present organellar defects, leading to a gradual decline in function during aging [1,2]. Autophagy is a highly regulated catabolic process that generally participates in cellular viability mechanisms under stress conditions, such as nutrient deprivation, hypoxia, endoplasmic reticulum stress, DNA damage, among others [9,10]. This process contributes to the renewal of cellular
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