Arora Rimpi B, Kumar Kushal, Deshmukh Rahul R
Department of Pharmacology, Neuropharmacology Division, ISF College of Pharmacy, Moga, Punjab, India.
Behav Pharmacol. 2013 Oct;24(7):580-9. doi: 10.1097/FBP.0b013e32836546db.
Upregulation in calcineurin (CaN) signaling has been implicated in various neurodegenerative disorders. In the present study, we have investigated the effect of FK506--a CaN inhibitor--on streptozotocin (STZ)-induced experimental dementia of the Alzheimer's type in rats. STZ was administered intracerebroventricularly to induce a cognitive deficit and oxidative stress. Nonimmunosuppressive doses (0.5 and 1 mg/kg postoperatively) of FK506 (tacrolimus) were administered for 21 day in STZ-treated rats. Cognitive functions were assessed using the Morris water maze and passive avoidance tasks. Malondialdehyde and nitrite glutathione levels, as well as acetylcholinesterase activity, were determined to evaluate oxidative stress and cholinergic functions. Lactate dehydrogenase levels were estimated and histological analysis of the dentate gyrus and the CA1 region of the hippocampus was carried out to identify degenerative changes. STZ produced significant deterioration of cognitive functions, oxidative stress, and degenerative changes in the cortical and hippocampal brain regions. FK506 dose-dependently attenuated STZ-induced cognitive deficits, oxidative stress, and degenerative changes in the cortex and hippocampus. These results suggest a potential role of CaN signaling in degenerative processes, and that inhibition of CaN may be useful in the treatment of neurodegenerative disorders such as Alzheimer's disease.
钙调神经磷酸酶（CaN）信号上调与多种神经退行性疾病有关。在本研究中，我们研究了CaN抑制剂FK506对链脲佐菌素（STZ）诱导的大鼠阿尔茨海默病型实验性痴呆的影响。通过脑室内注射STZ来诱导认知缺陷和氧化应激。在接受STZ治疗的大鼠中，给予非免疫抑制剂量（术后0.5和1 mg/kg）的FK506（他克莫司），持续21天。使用莫里斯水迷宫和被动回避任务评估认知功能。测定丙二醛和亚硝酸盐谷胱甘肽水平以及乙酰胆碱酯酶活性，以评估氧化应激和胆碱能功能。估计乳酸脱氢酶水平，并对齿状回和海马CA1区进行组织学分析，以确定退行性变化。STZ导致认知功能显著恶化、氧化应激以及皮质和海马脑区的退行性变化。FK506剂量依赖性地减轻了STZ诱导的认知缺陷、氧化应激以及皮质和海马的退行性变化。这些结果表明CaN信号在退行性过程中具有潜在作用，并且抑制CaN可能对治疗诸如阿尔茨海默病等神经退行性疾病有用。
