Department of Pharmacology, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria.
Neurophysiology Unit, Department of Physiology, Faculty of Basic Medical Sciences, PAMO University of Medical Sciences, Port-Harcourt, River State, Nigeria.
Metab Brain Dis. 2022 Dec;37(8):2807-2826. doi: 10.1007/s11011-022-01075-5. Epub 2022 Sep 3.
Cholinergic, oxidative, nitrergic alterations, and neuroinflammation are some key neuropathological features common in schizophrenia disease. They involve complex biological processes that alter normal behavior. The present treatments used in the management of the disorder remain ineffective together with some serious side effects as one of their setbacks. Taurine is a naturally occurring essential β-amino acid reported to elicit antipsychotic property in first episode psychosis in clinical setting, thus require preclinical investigation. Hence, we set out to investigate the effects of taurine in the prevention and reversal of ketamine-induced psychotic-like behaviors and the associated putative neurobiological mechanisms underlying its effects. Adult male Swiss mice were sheared into three separate cohorts of experiments (n = 7): drug alone, preventive and reversal studies. Treatments consisted of 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) with concomitant ketamine (20 mg/kg/i.p./day) injections between days 8-14, or 14 days entirely. Behavioral hyperactivity, despair, cognitive impairment, and catalepsy were measured. Brain oxidative/nitrergic imbalance, immunoreactivity (COX-2 and iNOS), and cholinergic markers were determined in the striatum, prefrontal-cortex, and hippocampus. Taurine abates ketamine-mediated psychotic-like episodes without cataleptogenic potential. Taurine attenuated ketamine-induced decrease in glutathione, superoxide-dismutase and catalase levels in the striatum, prefrontal-cortex and hippocampus. Also, taurine prevented and reversed ketamine-mediated elevation of malondialdehyde, nitrite contents, acetylcholinesterase activity, and suppressed COX-2 and iNOS expressions in a brain-region dependent manner. Conclusively, taurine insulates against ketamine-mediated psychotic phenotype by normalizing brain central cholinergic neurotransmissions, oxidative, nitrergic and suppression of immunoreactive proteins in mice brains.
胆碱能、氧化、硝化改变以及神经炎症是精神分裂症疾病中的一些关键神经病理学特征。它们涉及改变正常行为的复杂生物学过程。目前用于该疾病管理的治疗方法仍然无效，并且存在一些严重的副作用，这是其缺点之一。牛磺酸是一种天然存在的必需β-氨基酸，据报道在临床环境中具有抗精神病作用，因此需要进行临床前研究。因此，我们着手研究牛磺酸对预防和逆转氯胺酮诱导的精神病样行为及其潜在的神经生物学机制的影响。雄性瑞士成年小鼠被分为三组实验（n=7）：单独用药组、预防组和逆转组。治疗包括生理盐水（10mL/kg/天/口服）、牛磺酸（50 和 100mg/kg/天/口服）和利培酮（0.5mg/kg/天/口服），同时在第 8-14 天或第 14 天每天注射氯胺酮（20mg/kg/腹腔内注射）。测量行为多动、绝望、认知障碍和僵住。在纹状体、前额叶皮层和海马中测定脑氧化/硝化失衡、免疫反应（COX-2 和 iNOS）和胆碱能标志物。牛磺酸可减轻氯胺酮介导的精神病样发作，而无僵住作用。牛磺酸减弱了氯胺酮诱导的纹状体、前额叶皮层和海马中谷胱甘肽、超氧化物歧化酶和过氧化氢酶水平的降低。此外，牛磺酸以脑区依赖的方式预防和逆转氯胺酮介导的丙二醛、亚硝酸盐含量、乙酰胆碱酯酶活性升高，并抑制 COX-2 和 iNOS 的表达。总之，牛磺酸通过正常化大脑中枢胆碱能神经传递、氧化、硝化以及抑制小鼠大脑中的免疫反应蛋白，来防止氯胺酮介导的精神病表型。
