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Lack of Autophagy Induction by Lithium Decreases Neuroprotective Effects in the Striatum of Aged Rats
Pharmaceutics ( IF 5.4 ) Pub Date : 2021-01-21 , DOI: 10.3390/pharmaceutics13020135
Angelica Jardim Costa , Adolfo Garcia Erustes , Rita Sinigaglia , Carlos Eduardo Neves Girardi , Gustavo José da Silva Pereira , Rodrigo Portes Ureshino , Soraya Soubhi Smaili

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.

中文翻译:

锂缺乏自噬诱导降低老年大鼠纹状体的神经保护作用

自噬的药理调节被认为是一种有前途的神经保护策略。尽管已经假定锂调节该细胞过程,但尚未完全阐明与年龄有关的作用。在这里,我们评估了锂介导的年轻和老年纹状体的神经保护作用。在确定了用碳酸锂(Li 2 CO 3)诱导机车自噬的最佳实验条件后,我们用幼年和成年动物的大鼠脑纹状体切片测量了细胞活力,活性氧(ROS)生成和耗氧量。在年轻纹状体中,Li 2 CO 3提高组织活力并减少ROS生成。这些积极作用伴随着LC3-II,LAMP 1,Ambra 1和Beclin-1表达水平的提高。在老化的纹状体中,Li 2 CO 3降低了自噬通量并增加了基础耗氧率。摄入Li 2 CO 3 30天的老年大鼠纹状体的超微结构变化包括电子致密线粒体,cr裂紊乱,正常线粒体和溶酶体面积减少。我们的数据显示,年轻动物的纹状体受益于锂介导的神经保护作用,而老年大鼠的纹状体则没有。在制定涉及在衰老中诱导自噬的神经保护策略时,应考虑这些发现。
更新日期:2021-01-21
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