Title:Neuroprotective Effects of Agomelatine and Vinpocetine Against Chronic Cerebral Hypoperfusion Induced Vascular Dementia
Volume: 12
Issue: 3
Author(s): Surbhi Gupta, Prabhat Singh, Brij Mohan Sharma and Bhupesh Sharma
Affiliation:
Keywords:
2, 3, 5-triphenylterazolium chloride staining, acetylcholinesterase, brain damage, melatonin receptor, oxidative
stress, phosphodiesterase-1 enzyme, two vessel occlusion
Abstract: Chronic cerebral hypoperfusion (CCH) has been considered as a critical cause for the development of cognitive
decline and dementia of vascular origin. Melatonin receptors have been reported to be beneficial in improving memory
deterioration. Phosphodiesterase-1 (PDE1) enzyme offers protection against cognitive impairments and cerebrovascular
disorders. Aim of this study is to explore the role of agomelatine (a dual MT1 and MT2 melatonin receptor agonist) and
vinpocetine (selective PDE1 inhibitor) in CCH induced vascular dementia (VaD). Two vessel occlusion (2VO) or bilateral
common carotid arteries ligation method was performed to initiate a phase of chronic hypoperfusion in mice. 2VO animals
have shown significant cognitive deficits (Morris water maze), cholinergic dysfunction (increased acetyl cholinesterase
-AChE) activity alongwith increased brain oxidative stress (decreased brain catalase, glutathione, as well as superoxide
dismutase with an increase in malondialdehyde levels), and significant increase in brain infarct size (2,3,5-
triphenylterazolium chloride-TTC staining). Treatment of agomelatine and vinpocetine reduced CCH induced learning
and memory deficits and limited cholinergic dysfunction, oxidative stress, and tissue damage, suggesting that agomelatine
and vinpocetine may provide benefits in CCH induced VaD.