Reeta K H, Singh Devendra, Gupta Y K
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Neurochem Int. 2017 Sep;108:146-156. doi: 10.1016/j.neuint.2017.03.006. Epub 2017 Mar 8.
The present study investigated the neuroprotective effects of taurine, an essential amino acid for growth and development of central nervous system. Intracerebroventricular streptozotocin (ICV-STZ) model of cognitive impairment was used in male Wistar rats (270 ± 20 g). Morris water maze, elevated plus maze and passive avoidance paradigm were used to assess cognitive performance. Taurine (40, 60 and 120 mg/kg) was administered orally for 28 days following STZ administration on day 1. Oxidative stress parameters (malondialdehyde, glutathione, nitric oxide and superoxide dismutase) and cholinesterases (acetylcholinesterase and butyrylcholinesterase) activity were measured at end of the study in the cortex and hippocampus. Levels of TNF-α, IL-1β, expression of rho kinase-II (ROCK-II), glycogen synthase kinase-3β (GSK-3β) and choline acetyltransferase (ChAT) were studied in cortex and hippocampus. STZ caused significant cognitive impairment as compared to normal control. Chronic administration of taurine attenuated STZ-induced cognitive impairment. Increased oxidative stress and increased levels of TNF-α, IL-1β induced by STZ were also significantly attenuated by taurine. Taurine significantly (p < 0.05) decreased the STZ-induced increased expression of ROCK-II in cortex and hippocampus. Further, STZ-induced increased activity of cholinesterases was significantly (p < 0.001) mitigated by taurine. STZ decreased the expression of ChAT in hippocampus which was significantly (p < 0.05) reversed by taurine. However, GSK-3β expression was not altered by either STZ or taurine. The present study indicates that taurine exerts a neuroprotective role against STZ-induced cognitive impairment in rats. This effect is probably mediated by modulating oxidative stress, cholinesterases, inflammatory cytokines and expression of ROCK-II. Thus, this study suggests a potential of chronic taurine administration in cognitive impairment of Alzheimer's type.
本研究调查了牛磺酸对中枢神经系统生长发育所必需的一种氨基酸的神经保护作用。在雄性Wistar大鼠(270±20克)中采用脑室内注射链脲佐菌素(ICV-STZ)诱导认知障碍模型。使用莫里斯水迷宫、高架十字迷宫和被动回避范式来评估认知表现。在第1天给予STZ后,口服牛磺酸(40、60和120毫克/千克),持续28天。在研究结束时,测量皮质和海马中的氧化应激参数(丙二醛、谷胱甘肽、一氧化氮和超氧化物歧化酶)以及胆碱酯酶(乙酰胆碱酯酶和丁酰胆碱酯酶)活性。研究了皮质和海马中TNF-α、IL-1β的水平、rho激酶-II(ROCK-II)、糖原合酶激酶-3β(GSK-3β)和胆碱乙酰转移酶(ChAT)的表达。与正常对照组相比,STZ导致显著的认知障碍。长期给予牛磺酸可减轻STZ诱导的认知障碍。STZ诱导的氧化应激增加以及TNF-α、IL-1β水平升高也被牛磺酸显著减轻。牛磺酸显著(p<0.05)降低了STZ诱导的皮质和海马中ROCK-II表达增加。此外,STZ诱导的胆碱酯酶活性增加被牛磺酸显著(p<0.001)减轻。STZ降低了海马中ChAT的表达,而牛磺酸显著(p<0.05)使其逆转。然而,STZ和牛磺酸均未改变GSK-3β的表达。本研究表明,牛磺酸对STZ诱导大鼠认知障碍具有神经保护作用。这种作用可能是通过调节氧化应激、胆碱酯酶、炎性细胞因子和ROCK-II的表达介导的。因此,本研究提示长期给予牛磺酸对阿尔茨海默病型认知障碍具有潜在作用。