帕潘立酮棕榈酸酯
张力素
帕利哌酮
前额叶皮质
化学
神经保护
PTEN公司
神经科学
药理学
生物
PI3K/AKT/mTOR通路
细胞凋亡
医学
抗精神病药
精神分裂症(面向对象编程)
生物化学
精神科
认知
作者
Jiaxu Wang,Meng Li,Jing Zhang,Qing Gao,Zhaoxi Ding,Jinhao Sun
标识
DOI:10.1016/j.jad.2022.08.071
摘要
The putative mechanisms underlying the efficacy of the US Food and Drug Administration-approved antipsychotic drug paliperidone for the treatment of schizophrenia deserve additional investigation, which is the aim of the present animal study.The behavioral activities of mice were recorded in the open field test and light-dark box test. The effects of paliperidone on MK-801-induced neuronal damage in the prefrontal cortex were tested by flow cytometry, TUNEL staining assays, and ROS staining assays. The neuroprotective effects of paliperidone on neural dendrites and synapses were evaluated using Golgi staining and Sholl analysis. An adenovirus vector containing a Ca2+ indicator was used to monitor the calcium ion concentration in the prefrontal cortex. The expression levels of protein phosphatase 2A (PP2A) and phosphatase and tensin homolog (PTEN) were investigated using Western blotting.The data showed that MK-801 caused stereotyped behavior in mice and induced synaptic damage and dendritic spine impairment compared with the control, whereas paliperidone ameliorated these changes. Moreover, paliperidone reversed MK-801-induced decreases in PP2A and PTEN levels in prefrontal cortical neurons. Furthermore, in primary cultured cortical neurons and HT-22 cells, paliperidone inhibited cell apoptosis caused by MK-801. In particular, pretreatment with the PP2A inhibitor LB-100 significantly restrained the protective effects of paliperidone on MK-801-treated neurons and on locomotor activity and stereotypical behavior of mice.Whether other proteins are involved in this pathway and how the pathway works have not been revealed.Our data show that paliperidone alleviates neuronal damage induced by MK-801 via the PP2A/PTEN pathway.
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