title: Protective effect of transient receptor potential vanilloid subtype 1 (TRPV1) modulator, against behavioral, biochemical and structural damage in experimental models of Alzheimer's disease.
abstract: Alzheime's disease (AD) is an overwhelming neurodegenerative disorder, characterized by synaptic dysfunction, memory loss, neuro-inflammation and neural cell death. Very few treatments are in hand for the management of AD and they are only concentrating on peculiar aspects. Hence, an immense thrust is required to find utmost therapeutic targets to conquer this condition. This study investigates a potential role of vanillin, a selective agonist of transient receptor potential vanilloid subtype 1 (TRPV1) in the experimental models of AD viz. intracerebroventricular (i.c.v.) streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose induced AD in mice. The i.c.v. administration of STZ and intraperitoneally administration of AlCl3+d-galactose have significantly impaired learning-memory (Morris water maze and attentional set-shifting test), brain structure (hematoxylin, eosin and Congo red staining), enhanced brain oxidative stress (thiobarbituric acid reactive substance - TBARS and glutathione - GSH), nitrosative stress (nitrite/nitrate), acetylcholinesterase activity (AChE), inflammation (MPO), and calcium levels (Ca(++)). Treatment with vanillin in different doses and donepezil have significantly ameliorated i.c.v. STZ and AlCl3+d-galactose induced reduction in executive function, impaired reversal learning, cognition, memory and brain damage. Treatment with these drugs has also reduced the brain oxidative stress (TBARS and GSH), nitrosative stress (nitrite/nitrate), and AChE, MPO, and Ca(++) levels. These results indicate that vanillin, a selective agonist of TRPV1 and donepezil, a potent acetylcholine esterase inhibitor have attenuated i.c.v. STZ and AlCl3+d-galactose induced experimental AD. Hence, pharmacological positive modulation of TRPV1 channels may be a potential research target for mitigation of AD.
authors.affiliation: Department of Pharmacology, School of Pharmacy, BIT, 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, BIT, Meerut, Uttar Pradesh, India. Electronic address: sharmaslab2@gmail.com.
authors.forename: B M
authors.initials: BM
authors.lastname: Sharma
authors.affiliation: Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Uttar Pradesh, India; Conscience Research, Delhi, 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 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002712:Chlorides; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005690:Galactose; D007189:Indans / Q000494:pharmacology; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D013311:Streptozocin; D050916:TRPV Cation Channels / Q000819:agonists* / Q000378:metabolism
chemical_list: D017607:Aluminum Compounds; D001547:Benzaldehydes; D002712:Chlorides; D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010880:Piperidines; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000077410:Aluminum Chloride; D013311:Streptozocin; D000077265:Donepezil; C100058:vanillin; D005690:Galactose
keywords: Aluminum trichloride; Attentional set-shifting test; Congo red staining; Morris water maze; Streptozotocin; Vanillin