Jayant Shalini, Sharma Brij Mohan, Bansal Rani, Sharma Bhupesh
Neuropharmacology Lab., Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India.
Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India.
Pharmacol Biochem Behav. 2016 Jan;140:39-50. doi: 10.1016/j.pbb.2015.11.006. Epub 2015 Nov 11.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that pervasively affects the population across the world. Currently, there is no effective treatment available for this and existing drugs merely slow the progression of cognitive function decline. Thus, massive effort is required to find an intended therapeutic target to overcome this condition. The present study has been framed to investigate the ameliorative role of selective modulator of cannabinoid receptor type 2 (CB2), 1-phenylisatin in experimental AD condition. We have induced experimental AD in mice by using two induction models viz., intracerebroventricular (i.c.v.) administration of streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose. Morris water maze (MWM) and attentional set shifting test (ASST) were used to assess learning and memory. Hematoxylin-eosin and Congo red staining were used to examine the structural variation in brain. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), nitric oxide levels (nitrites/nitrates), acetyl cholinesterase activity, myeloperoxidase and calcium levels were also estimated. i.c.v. STZ as well as AlCl3+d-galactose have impaired spatial and reversal learning with executive functioning, increased brain oxidative and nitrosative stress, cholinergic activity, inflammation and calcium levels. Furthermore, these agents have also enhanced the burden of Aβ plaque in the brain. Treatment with 1-phenylisatin and donepezil attenuated i.c.v. STZ as well as AlCl3+d-galactose induced impairment of learning-memory, brain biochemistry and brain damage. Hence, this study concludes that CB2 receptor modulation can be a potential therapeutic target for the management of AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，广泛影响着全球人口。目前，针对该病尚无有效的治疗方法，现有的药物只能减缓认知功能衰退的进程。因此，需要付出巨大努力来寻找理想的治疗靶点以攻克这一病症。本研究旨在探讨大麻素2型受体（CB2）的选择性调节剂1-苯基异吲哚在实验性AD条件下的改善作用。我们通过两种诱导模型在小鼠中诱导实验性AD，即脑室内（i.c.v.）注射链脲佐菌素（STZ）以及氯化铝（AlCl3）+D-半乳糖。采用莫里斯水迷宫（MWM）和注意力转换测试（ASST）来评估学习和记忆。使用苏木精-伊红染色和刚果红染色来检查大脑的结构变化。还测定了脑氧化应激（硫代巴比妥酸反应性物质和谷胱甘肽）、一氧化氮水平（亚硝酸盐/硝酸盐）、乙酰胆碱酯酶活性、髓过氧化物酶和钙水平。i.c.v.注射STZ以及AlCl3+D-半乳糖损害了空间学习和逆向学习以及执行功能，增加了脑氧化应激和亚硝化应激、胆碱能活性、炎症反应和钙水平。此外，这些药物还增加了大脑中Aβ斑块的负担。用1-苯基异吲哚和多奈哌齐治疗减轻了i.c.v.注射STZ以及AlCl3+D-半乳糖诱导的学习记忆损害、脑生化改变和脑损伤。因此，本研究得出结论，CB2受体调节可能是治疗AD的一个潜在治疗靶点。
