title: Pharmacological benefits of selective modulation of cannabinoid receptor type 2 (CB2) in experimental Alzheimer's disease.
abstract: 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.
authors.affiliation: Neuropharmacology Lab., Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India. Electronic address: sharmaslab4@gmail.com.
authors.forename: Shalini
authors.initials: S
authors.lastname: Jayant
authors.affiliation: Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India. Electronic address: sharmaslab1@gmail.com.
authors.forename: Brij Mohan
authors.initials: BM
authors.lastname: Sharma
authors.affiliation: Department of Pathology, Swami Vivekanand Subharti University, Subharti Puram, NH-58, Delhi Haridwar Bypass, Meerut, Uttar Pradesh, India.
authors.forename: Rani
authors.initials: R
authors.lastname: Bansal
authors.affiliation: Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Sector-125, Noida, Uttar Pradesh, India; CNS and CVS Pharmacology, Conscience Research, Pocket F-233, B, Dilshad Garden, Delhi 110095, India. Electronic address: drbhupeshresearch@gmail.com.
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Sharma
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology*; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002712:Chlorides; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005690:Galactose; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D058225:Plaque, Amyloid / Q000473:pathology; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects*; D013311:Streptozocin
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D043885:Receptor, Cannabinoid, CB2; D000077410:Aluminum Chloride; D013311:Streptozocin; D005690:Galactose
keywords: 1-Phenylisatin; Aluminum trichloride; Attentional set shifting test; Image J; Morris water maze; Myeloperoxidase; Streptozotocin