Modulation of Transient Receptor Potential Vanilloid Subtype 1 (TRPV1) and Norepinephrine Transporters (NET) Protect Against Oxidative Stress, Cellular Injury, and Vascular Dementia
Overview
Neurology
Affiliations
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.
Deval C, Sharma P, Sharma B, Singh B Clin Psychopharmacol Neurosci. 2025; 23(1):120-132.
PMID: 39820118 PMC: 11747741. DOI: 10.9758/cpn.24.1216.
Sharma P, Sharma B, Kharkwal H, Ghildiyal S, Patil V Metab Brain Dis. 2024; 40(1):33.
PMID: 39570531 DOI: 10.1007/s11011-024-01470-0.
Sharma P, Gaur N, Jayant S, Sharma B, Singh B, Kharkwal H Pharmacol Rep. 2022; 74(3):481-492.
PMID: 35396697 DOI: 10.1007/s43440-022-00364-1.
Block of Voltage-Gated Sodium Channels by Atomoxetine in a State- and Use-dependent Manner.
Fohr K, Nastos A, Fauler M, Zimmer T, Jungwirth B, Messerer D Front Pharmacol. 2021; 12:622489.
PMID: 33732157 PMC: 7959846. DOI: 10.3389/fphar.2021.622489.
Lagunin A, Ivanov S, Gloriozova T, Pogodin P, Filimonov D, Kumar S Sci Rep. 2020; 10(1):257.
PMID: 31937840 PMC: 6959222. DOI: 10.1038/s41598-019-57199-9.