title: Modulation of transient receptor potential vanilloid subtype 1 (TRPV1) and norepinephrine transporters (NET) protect against oxidative stress, cellular injury, and vascular dementia.
abstract: Chronic cerebral hypoperfusion (CCH) is a risk factor for the development of vascular dementia (VaD). CCH participates in a negative role in cognitive impairments. Transient receptor potential vanilloid subtype 1 (TRPV1) participates in cognition, ischemic damage and neuroprotection. Selective norepinephrine transporter (NET) inhibitors have a role in cognitive dysfunction and oxidative stress. The role of TRPV1 and NET in CCH induced VaD is still unknown. The present study has been structured to investigate the role of vanillin; a selective agonist of TRPV1 as well as atomoxetine; a selective NET inhibitor in CCH induced VaD in mice. Permanent bilateral common carotid arteries ligation or two vessel occlusion (2VO) technique was used to induce a stage of chronic cerebral hypoperfusion in mice. 2VO animals have shown significant impairment of locomotion (Actophotometer), motor coordination (Rota rod), learning and memory (Morris water maze). 2VO animals have shown significant reduction in brain catalase, glutathione, and superoxide dismutase, with significant increase in brain infarct size (TTC staining), malondialdehyde and acetyl cholinesterase-AChE activity. Whereas, administration of vanillin as well as atomoxetine has significantly attenuated 2VO induced impaired locomotion, motor coordination, learning and memory, brain damage, brain oxidative stress and higher AChE activity. It may be concluded that 2VO induced CCH has elicited VaD, which was attenuated by vanillin and atomoxetine. Thus, modulators of vanilloid receptors and norepinephrine transporter may be explored further for their benefits in CCH induced VaD.
authors.forename: Surbhi
authors.initials: S
authors.lastname: Gupta
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Sharma
authors.forename: Prabhat
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India. drbhupeshresearch@gmail.com.
authors.forename: Brij Mohan
authors.initials: BM
authors.lastname: Sharma
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D000069445:Atomoxetine Hydrochloride; D001547:Benzaldehydes / Q000494:pharmacology; D001921:Brain / Q000098:blood supply; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D015140:Dementia, Vascular / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D011437:Propylamines / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000975:Antioxidants; D001547:Benzaldehydes; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011437:Propylamines; C493228:Slc6a2 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000069445:Atomoxetine Hydrochloride; C100058:vanillin