Lithium produces bi-directionally regulation of mood disturbance, acts synergistically with anti-depressive/-manic agents, and did not deteriorate the cognitive impairment in murine model of bipolar disorder.
Lithium produces bi-directionally regulation of mood disturbance, acts synergistically with anti-depressive/-manic agents, and did not deteriorate the cognitive impairment in murine model of bipolar disorder.
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锂对情绪障碍产生双向调节作用，与抗抑郁/躁狂药物协同作用，并且不会恶化双相情感障碍小鼠模型的认知障碍
DOI：
10.1038/s41398-022-02087-6
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发表时间：
2022-09-02
影响因子：
6.8
通讯作者：
Song, Xueqin
中科院分区：
文献类型：
--
作者：
Zhuo, Chuanjun;Zhou, Chunhua;Tian, Hongjun;Li, Qianchen;Chen, Jiayue;Yang, Lei;Zhang, Qiuyu;Li, Ranli;Ma, Xiaoyan;Cai, Ziyao;Chen, Guangdong;Xu, Yong;Song, Xueqin
锂（Li）是一种公认的情绪障碍治疗方法，可能具有神经保护作用。Li的双向调节（即影响躁狂症状和抑郁症状）尚未得到证实。本研究探讨：(1)Li在抑郁、躁狂症和双相情感障碍（BP）小鼠模型中的双向调节作用；(2)与抗抑郁/抗躁狂药物的潜在Li协同作用。采用慢性不可预测轻度应激（CUMS）和氯胺酮诱发躁狂症（KM）模型。将这些方法串联起来，得到一个BP模型。体内双光子成像用于可视化Ca2+活动在背外侧前额叶皮层。抑郁、躁狂和认知功能分别通过强迫游泳任务（FST）、开放领域活动任务（OFA）和新物体识别任务进行评估。在CUMS小鼠中，Li可增强Ca2+活性，而lamotriine （LTG）或valproate （VPA）可减弱Li和VPA单药治疗的效果；Li或LTG可减弱FST的抑制性不动，LTG- vpa或LTG-Li的减弱作用更强；Li和LTG-Li对新目标的探索增强，而LTG、VPA和LTG-VPA对新目标的探索减弱。在KM小鼠中，Li或VPA减轻了OFA躁狂症状并部分正常化了Ca2+活性；Li改善了认知功能，而VPA加重了KM的改变。这些模式在各自的BP模型阶段被复制。锂具有双向的情绪调节作用和认知支持作用，尽管这种作用很弱。Li与抗抑郁药/躁狂药合用可增强情绪调节功效，同时减弱其认知损害作用。
Lithium (Li) is a well-established mood disorder treatment and may be neuroprotective. Bi-directional regulation (i.e. affecting manic symptoms and depressive symptoms) by Li has not been demonstrated. This study explored: (1) bidirectional regulation by Li in murine models of depression, mania, and bipolar disorder (BP); and (2) potential Li synergism with antidepressant/anti-mania agents. The chronic unpredictable mild stress (CUMS) and ketamine-induced mania (KM) models were used. These methods were used in series to produce a BP model. In vivo two-photon imaging was used to visualize Ca2+ activity in the dorsolateral prefrontal cortex. Depressiveness, mania, and cognitive function were assessed with the forced swim task (FST), open field activity (OFA) task, and novel object recognition task, respectively. In CUMS mice, Ca2+ activity was increased strongly by Li and weakly by lamotrigine (LTG) or valproate (VPA), and LTG co-administration reduced Li and VPA monotherapy effects; depressive immobility in the FST was attenuated by Li or LTG, and attenuated more strongly by LTG-VPA or LTG-Li; novel object exploration was increased strongly by Li and weakly by LTG-Li, and reduced by LTG, VPA, or LTG-VPA. In KM mice, Li or VPA attenuated OFA mania symptoms and normalized Ca2+ activity partially; Li improved cognitive function while VPA exacerbated the KM alteration. These patterns were replicated in the respective BP model phases. Lithium had bi-directional, albeit weak, mood regulation effects and a cognitive supporting effect. Li co-administration with antidepressant/-manic agents enhanced mood-regulatory efficacy while attenuating their cognitive-impairing effects.
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