Protective effect of transient receptor potential vanilloid subtype 1 (TRPV1) modulator, against behavioral, biochemical and structural damage in experimental models of Alzheimer's disease
| Autor: | Bikash Sharma, Bhupesh Sharma, Shalini Jayant |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Drug Evaluation Preclinical TRPV1 TRPV Cation Channels Morris water navigation task Brain damage Pharmacology medicine.disease_cause Streptozocin Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Chlorides Piperidines Alzheimer Disease medicine TBARS Aluminum Chloride Animals Donepezil Aluminum Compounds Molecular Biology Nootropic Agents Dose-Response Relationship Drug Chemistry General Neuroscience Brain Galactose Acetylcholinesterase Disease Models Animal Neuroprotective Agents 030104 developmental biology Biochemistry Benzaldehydes Indans Cholinesterase Inhibitors Neurology (clinical) medicine.symptom 030217 neurology & neurosurgery Oxidative stress Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 1642:397-408 |
| ISSN: | 0006-8993 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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