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.