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牛磺酸可预防 MK-801 诱导的斑马鱼集群分散和皮质醇反应改变。

Taurine prevents MK-801-induced shoal dispersion and altered cortisol responses in zebrafish.

机构信息

Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria. 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil.

Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria. 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2021 Dec 20;111:110399. doi: 10.1016/j.pnpbp.2021.110399. Epub 2021 Jul 9.

Abstract

Schizophrenia is a chronic neuropsychiatric disorder characterized by a shortened lifespan and significant impaired social and vocational functioning. Schizophrenic patients can present hypothalamic-pituitary-adrenal (HPA) axis dysfunctions and cortisol dysregulation, which play an important role on the etiology onset, exacerbation, and relapsing of symptoms. Based on its intrinsic neuroprotective properties, taurine is considered a promising substance with beneficial role on various brain disorders, including schizophrenia. Here, we evaluated the effects of taurine on shoaling behavior and whole-body cortisol levels in zebrafish treated with dizocilpine (MK-801), which elicits schizophrenia-like phenotypes in animal models. Briefly, zebrafish shoals (4 fish per shoal) were exposed to dechlorinated water or taurine (42, 150, or 400 mg/L) for 60 min. Then, saline (PBS, pH 7.4 or 2.0 mg/kg MK-801) were intraperitoneally injected and zebrafish behavior was recorded 15 min later. In general, MK-801 disrupted shoaling behavior and reduced whole-body cortisol levels in zebrafish. All taurine pretreatments prevented MK-801-induced increase in shoal area, while 400 mg/L taurine prevented the MK-801-induced alterations in neuroendocrine responses. Moreover, all taurine-pretreated groups showed increased geotaxis, supporting a modulatory role in the overall dispersion pattern of the shoal. Collectively, our novel findings show a potential protective effect of taurine on MK-801-induced shoal dispersion and altered neuroendocrine responses, fostering the use of zebrafish models to assess schizophrenia-like phenotypes.

摘要

精神分裂症是一种慢性神经精神障碍,其特征是寿命缩短,社会和职业功能显著受损。精神分裂症患者可能表现出下丘脑-垂体-肾上腺(HPA)轴功能障碍和皮质醇失调,这对病因发病、恶化和症状复发起着重要作用。基于其内在的神经保护特性,牛磺酸被认为是一种有前途的物质,对包括精神分裂症在内的各种脑疾病具有有益作用。在这里,我们评估了牛磺酸对用地卓西平(MK-801)处理的斑马鱼的群居行为和全身皮质醇水平的影响,MK-801 在动物模型中引发类似精神分裂症的表型。简而言之,将斑马鱼群(每群 4 条鱼)暴露于去氯水中或牛磺酸(42、150 或 400mg/L)中 60 分钟。然后,腹膜内注射生理盐水(PBS,pH7.4 或 2.0mg/kg MK-801),并在 15 分钟后记录斑马鱼的行为。一般来说,MK-801 破坏了斑马鱼的群居行为并降低了全身皮质醇水平。所有牛磺酸预处理均阻止了 MK-801 诱导的群体面积增加,而 400mg/L 牛磺酸阻止了 MK-801 诱导的神经内分泌反应改变。此外,所有牛磺酸预处理组的趋地性均增加,支持对群体整体分散模式的调节作用。总的来说,我们的新发现表明牛磺酸对 MK-801 诱导的群体分散和改变的神经内分泌反应具有潜在的保护作用,促进了使用斑马鱼模型来评估类似精神分裂症的表型。

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