Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
Indian J Pharmacol. 2012 May;44(3):366-71. doi: 10.4103/0253-7613.96337.
Streptozotocin (STZ) and sodium nitrite (NaNO(2)) treatment have been positively correlated with higher incidence of memory loss and experimental dementia. The present study was designed to investigate the potential of the Riluzole, an inhibitor of glutamatergic neurotransmission and activator of TWIK-Related K(+) channels with incidences of memory deficits associated with dementia in mice.
Dementia was induced in Swiss albino mice by intracerebroventricular STZ (ICV) and by subcutaneous NaNO(2) in separate groups of animals. Morris water maze was employed to assess learning and memory of the animals. Biochemical analysis of brain homogenate was performed so as to assess brain acetyl cholinesterase (AChE) activity. Brain thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured to assess total oxidative stress.
Treatment of ICV STZ and NaNO(2) produced a significant decrease in water maze performance of mice hence reflecting loss of learning and memory. Furthermore, higher levels of brain AChE activity and oxidative stress were observed in these animals. Administration of riluzole (5 and 10 mg/kg intraperitoneally) successfully attenuated memory deficits as well as ICV STZ- and NaNO(2) -induced changes in the levels of brain AChE, TBARS, and GSH.
The memory restorative effects of riluzole in dementia may involve its multiple functions including anti-oxidative and anticholinesterase properties.
链脲佐菌素(STZ)和亚硝酸钠(NaNO2)的处理与记忆丧失和实验性痴呆的发生率升高呈正相关。本研究旨在研究利鲁唑(一种谷氨酸能神经传递抑制剂和 TWIK 相关 K+通道激活剂)对与痴呆相关的记忆缺陷的潜在作用,该药物已应用于小鼠。
通过侧脑室 STZ(ICV)和皮下 NaNO2 在单独的动物组中诱导痴呆。采用 Morris 水迷宫评估动物的学习和记忆能力。对脑匀浆进行生化分析,以评估脑乙酰胆碱酯酶(AChE)活性。测量脑硫代巴比妥酸反应性物质(TBARS)水平和还原型谷胱甘肽(GSH)水平,以评估总氧化应激。
ICV STZ 和 NaNO2 的治疗导致小鼠在水迷宫中的表现显著下降,反映出学习和记忆的丧失。此外,这些动物的大脑 AChE 活性和氧化应激水平更高。利鲁唑(腹腔内 5 和 10mg/kg)的给药成功减轻了记忆缺陷,以及 ICV STZ 和 NaNO2 诱导的大脑 AChE、TBARS 和 GSH 水平的变化。
利鲁唑在痴呆中的记忆恢复作用可能与其多种功能有关,包括抗氧化和抗胆碱酯酶特性。