Adjunctive clozapine with bright light mitigates cognitive deficits by synaptic plasticity and neurogenesis in sub-chronic MK-801 treated mice

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES Pharmacology Biochemistry and Behavior Pub Date : 2024-07-11 DOI:10.1016/j.pbb.2024.173821

Lizhi Zhang , Yiying Zhou , Yanhong Xie , Yudong Ying , Yan Li , Sen Ye , Zhengchun Wang

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Abstract

Schizophrenia impacts about 1 % of the global population, with clozapine (CLZ) being a critical treatment for refractory cases despite its limitations in effectiveness and adverse effects. Therefore, the search for more effective treatments remains urgent. Light treatment (LT) recognized for enhancing cognition and mood, presents a promising complementary approach. This study investigated the effects of CLZ and LT on cognitive impairments in a sub-chronic MK-801 induced schizophrenia mouse model. Results showed that both CLZ and CLZ + LT treatment elevate cognitive performance of sub-chronic MK-801 treated mice in serial behavioral tests over two months. Histological analysis revealed increased dendritic spine density and branching, and synaptic repair in the hippocampus with CLZ and CLZ + LT interventions. Furthermore, both treatments increased brain-derived neurotrophic factor (BDNF) expression in the hippocampus, likely contributing to cognitive amelioration in MK-801 treated mice. Additionally, BrdU labeling revealed that CLZ + LT further enhances neurogenesis in the dentate gyrus (DG) and lateral ventricle (LV) of sub-chronic MK-801 treated mice. These findings may have implications for the development of noninvasive and adjunctive treatment strategies aimed at alleviating cognitive impairments and improving functional outcomes in individuals with schizophrenia.

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在亚慢性 MK-801 治疗的小鼠中，氯氮平与强光的辅助作用可通过突触可塑性和神经发生减轻认知缺陷。

精神分裂症影响着全球约 1% 的人口，氯氮平（CLZ）是治疗难治性病例的关键药物，尽管它在有效性和不良反应方面存在局限性。因此，寻找更有效的治疗方法仍然迫在眉睫。光照疗法（LT）被认为能增强认知和情绪，是一种很有前景的补充方法。本研究调查了CLZ和LT对亚慢性MK-801诱导的精神分裂症小鼠模型认知障碍的影响。结果表明，CLZ 和 CLZ + LT 治疗均可提高亚慢性 MK-801 治疗小鼠在两个月的连续行为测试中的认知能力。组织学分析表明，CLZ和CLZ + LT干预可增加树突棘密度和分支，并修复海马突触。此外，这两种治疗方法都增加了海马中脑源性神经营养因子（BDNF）的表达，这可能有助于MK-801治疗小鼠认知能力的改善。此外，BrdU标记显示，CLZ + LT可进一步增强亚慢性MK-801治疗小鼠齿状回（DG）和侧脑室（LV）的神经发生。这些发现可能对开发旨在减轻精神分裂症患者认知障碍和改善其功能预后的非侵入性辅助治疗策略具有重要意义。

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来源期刊

Pharmacology Biochemistry and Behavior 医学-行为科学

CiteScore

6.40

自引率

2.80%

发文量

122

审稿时长

38 days

期刊介绍： Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.