Schizophrenia is a life disabling, multisystem neuropsychiatric disease mostly derived from complex epigenetic-mediated neurobiological changes causing behavioural deficits. Neurochemical disorganizations, neurotrophic and neuroimmune alterations are some of the challenging neuropathologies proving unabated during psychopharmacology of schizophrenia, further bedeviled by drug-induced metabolic derangements including alteration of amino acids. In first-episode schizophrenia patients, taurine, an essential β-amino acid represses psychotic-symptoms. However, its anti-psychotic-like mechanisms remain incomplete. This study evaluated the ability of taurine to prevent or reverse ketamine-induced experimental psychosis and the underlying neurochemical, neurotrophic and neuroinmune mechanisms involved in taurine’s clinical action. The study consisted of three different experiments with Swiss mice (n = 7). In the drug alone, mice received saline (10 mL/kg/p.o./day), taurine (50 and 100 mg/kg/p.o./day) and risperidone (0.5 mg/kg/p.o./day) for 14 days. In the preventive study of separate cohort, mice were concomitantly given ketamine (20 mg/kg/i.p./day) from days 8 to 14. In the reversal study, mice received ketamine for 14 days before taurine or risperidone treatments from days 8 to 14 respectively. Afterwards, stereotypy behaviour, social, non-spatial memory deficits, and body weights were assessed. Neurochemical (dopamine, 5-hydroxytryptamine, glutamic acid decarboxylase, (GAD)), brain derived-neurotrophic factor (BDNF) and pro-inflammatory cytokines [tumor necrosis factor-alpha, (TNF-α), interleukin-6, (IL-6)] were assayed in the striatum, prefrontal-cortex and hippocampal area. Taurine attenuates ketamine-induced schizophrenia-like behaviour without changes in body weight. Taurine reduced ketamine-induced dopamine and 5-hydroxytryptamine changes, and increased GAD and BDNF levels in the striatum, prefrontal-cortex and hippocampus, suggesting increased GABAergic and neurotrophic transmissions. Taurine decreases ketamine-induced increased in TNF-α and IL-6 concentrations in the striatum, prefrontal-cortex and hippocampus. These findings also suggest that taurine protects against schizophrenia through neurochemical modulations, neurotrophic enhancement, and inhibition of neuropathologic cytokine activities.

精神分裂症是一种致残性多系统神经精神疾病，主要源于复杂的表观遗传介导的神经生物学变化，导致行为缺陷。神经化学紊乱、神经营养和神经免疫改变是一些具有挑战性的神经病理学，在精神分裂症的精神药理学中被证明有增无减，进一步受到药物诱导的代谢紊乱（包括氨基酸改变）的困扰。在首发精神分裂症患者中，牛磺酸是一种必需的 β-氨基酸，可抑制精神病-症状。然而，它的抗精神病样机制仍然不完整。本研究评估了牛磺酸预防或逆转氯胺酮诱发的实验性精神病的能力，以及牛磺酸临床作用中涉及的潜在神经化学、神经营养和神经免疫机制。该研究包括三个不同的瑞士小鼠实验（n = 7). 仅在药物中，小鼠接受生理盐水（10 mL/kg/po/天）、牛磺酸（50 和 100 mg/kg/po/天）和利培酮（0.5 mg/kg/po/天），持续 14 天。在单独队列的预防性研究中，小鼠从第 8 天到第 14 天同时给予氯胺酮（20 mg/kg/ip/天）。在逆转研究中，小鼠在第 8 天到第 14 天接受牛磺酸或利培酮治疗前接受氯胺酮 14 天分别。之后，对刻板行为、社交、非空间记忆缺陷和体重进行了评估。神经化学物质（多巴胺、5-羟色胺、谷氨酸脱羧酶 (GAD)）、脑源性神经营养因子 (BDNF) 和促炎细胞因子 [肿瘤坏死因子-α、(TNF-α)、白介素-6、(IL- 6)] 在纹状体、前额皮质和海马区进行了检测。牛磺酸在不改变体重的情况下减轻氯胺酮诱导的精神分裂症样行为。牛磺酸减少了氯胺酮诱导的多巴胺和 5-羟色胺变化，并增加了纹状体、前额叶皮质和海马体中的 GAD 和 BDNF 水平，表明增加了 GABA 能和神经营养传递。牛磺酸可降低氯胺酮引起的纹状体、前额叶皮质和海马体中 TNF-α 和 IL-6 浓度的升高。这些发现还表明，牛磺酸通过神经化学调节、神经营养增强和神经病理细胞因子活性的抑制来预防精神分裂症。暗示增加的 GABA 能和神经营养传递。牛磺酸可降低氯胺酮引起的纹状体、前额叶皮质和海马体中 TNF-α 和 IL-6 浓度的升高。这些发现还表明，牛磺酸通过神经化学调节、神经营养增强和神经病理细胞因子活性的抑制来预防精神分裂症。暗示增加的 GABA 能和神经营养传递。牛磺酸可降低氯胺酮引起的纹状体、前额叶皮质和海马体中 TNF-α 和 IL-6 浓度的升高。这些发现还表明，牛磺酸通过神经化学调节、神经营养增强和神经病理细胞因子活性的抑制来预防精神分裂症。