Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well as suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways and biologic systems, the precise mechanism through which lithium stabilizes mood remains elusive. Furthermore, there is recent support for the therapeutic potential of lithium in other brain diseases. This review offers a comprehensive examination of contemporary understanding and predominant theories concerning the diverse mechanisms underlying lithium’s effects. These findings are based on investigations utilizing cellular and animal models of neurodegenerative and psychiatric disorders. Recent studies have provided additional support for the significance of glycogen synthase kinase-3 (GSK3) inhibition as a crucial mechanism. Furthermore, research has shed more light on the interconnections between GSK3-mediated neuroprotective, antioxidant, and neuroplasticity processes. Moreover, recent advancements in animal and human models have provided valuable insights into how lithium-induced modifications at the homeostatic synaptic plasticity level may play a pivotal role in its clinical effectiveness. We focused on findings from translational studies suggesting that lithium may interface with microRNA expression. Finally, we are exploring the repurposing potential of lithium beyond bipolar disorder. These recent findings on the therapeutic mechanisms of lithium have provided important clues toward developing predictive models of response to lithium treatment and identifying new biologic targets.

中文翻译：

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锂药理学和毒理学的新进展：神经生物学导向的概述


在过去的六十年中，锂被认为是长期治疗双相情感障碍的黄金标准治疗方法，因为它可以有效预防躁狂和抑郁发作以及自杀行为。然而，尽管锂对各种细胞途径和生物系统有大量观察到的影响，但其稳定情绪的确切机制仍然难以捉摸。此外，最近有人支持锂在其他脑部疾病中的治疗潜力。这篇综述对有关锂效应的不同机制的当代理解和主流理论进行了全面的审视。这些发现基于利用神经退行性和精神疾病的细胞和动物模型的研究。最近的研究为糖原合酶激酶 3 (GSK3) 抑制作为关键机制的重要性提供了额外的支持。此外，研究进一步揭示了 GSK3 介导的神经保护、抗氧化和神经可塑性过程之间的相互联系。此外，动物和人类模型的最新进展为锂诱导的稳态突触可塑性修饰如何在其临床有效性中发挥关键作用提供了宝贵的见解。我们重点关注转化研究的结果，表明锂可能与 microRNA 表达相互作用。最后，我们正在探索锂在双相情感障碍之外的再利用潜力。这些关于锂治疗机制的最新发现为开发锂治疗反应的预测模型和识别新的生物靶点提供了重要线索。