Capsaicin alleviates neuronal apoptosis and schizophrenia-like behavioral abnormalities induced by early life stress.

IF 3 Q2 PSYCHIATRY
Shilin Xu, Keke Hao, Ying Xiong, Rui Xu, Huan Huang, Huiling Wang
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Abstract

Early life stress (ELS) is associated with the later development of schizophrenia. In the rodent model, the maternal separation (MS) stress may induce neuronal apoptosis and schizophrenia-like behavior. Although the TRPV1 agonist capsaicin (CAP) has been reported to reduce apoptosis in the central nervous system, its effect in MS models is unclear. Twenty-four hours of MS of Wistar rat pups on postnatal day (PND9) was used as an ELS. Male rats in the adult stage were the subjects of the study. CAP (1 mg/kg/day) intraperitoneal injection pretreatment was undertaken before behavioral tests for 1 week and continued during the tests. Behavioral tests included open field, novel object recognition, Barnes maze test, and pre-pulse inhibition (PPI) test. MS rats showed behavioral deficits and cognitive impairments mimicking symptoms of schizophrenia compared with controls. MS decreased the expression of TRPV1 in the frontal association cortex (FrA) and in the hippocampal CA1, CA3, and dentate gyrus (DG) regions compared with the control group resulting in the increase of pro-apoptotic proteins (BAX, Caspase3, Cleaved-Caspase3) and the decrease of anti-apoptotic proteins (Bcl-2). The number of NeuN++TUNEL+ cells increased in the MS group in the FrA, CA1, CA3, and DG compared with the control group. Neuronal and behavioral impairments of MS were reversed by treatment with CAP. Exposure to ELS may lead to increased neuronal apoptosis and impaired cognitive function with decreased TRPV1 expression in the prefrontal cortex and hippocampus in adulthood. Sustained low-dose administration of CAP improved neuronal apoptosis and cognitive function. Our results provide evidence for future clinical trials of chili peppers or CAP as dietary supplements for the reversal treatment of schizophrenia.

Abstract Image

辣椒素可减轻早期生活压力引起的神经元凋亡和精神分裂症样行为异常。
早期生活压力(ELS)与精神分裂症的后期发展有关。在啮齿类动物模型中,母体分离(MS)应激可能诱导神经元凋亡和精神分裂症样行为。尽管TRPV1激动剂辣椒素(CAP)已被报道可减少中枢神经系统的细胞凋亡,但其在MS模型中的作用尚不清楚。Wistar大鼠幼崽在出生后24小时的MS(PND9)用作ELS。成年期雄性大鼠为研究对象。帽(1 mg/kg/天)腹膜内注射预处理1周,并在测试期间继续。行为测试包括开放视野、新物体识别、巴恩斯迷宫测试和脉冲前抑制(PPI)测试。与对照组相比,MS大鼠表现出类似精神分裂症症状的行为缺陷和认知障碍。与对照组相比,MS降低了额相关皮层(FrA)和海马CA1、CA3和齿状回(DG)区域TRPV1的表达,导致促凋亡蛋白(BAX、Caspase3、Cleaved-Caspase3)增加和抗凋亡蛋白(Bcl-2)减少。与对照组相比,MS组FrA、CA1、CA3和DG中NeuN++TUNEL+细胞的数量增加。多发性硬化症的神经元和行为障碍通过CAP治疗得以逆转。暴露于ELS可能导致神经元凋亡增加和认知功能受损,成年后前额叶皮层和海马中TRPV1的表达减少。持续低剂量给予CAP可改善神经元凋亡和认知功能。我们的研究结果为辣椒或CAP作为膳食补充剂逆转治疗精神分裂症的未来临床试验提供了证据。
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