Neuroprotective effect of selective DPP-4 inhibitor in experimental vascular dementia.

Autor: Jain S; CNS and CVS Lab., Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Pin-250103, Uttar Pradesh, India; Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, A-Block, Ground Floor, Sector-125, Noida - 201303, Uttar Pradesh, India. Electronic address: sharmaslab6@gmail.com., Sharma B; School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Pin-250103, Uttar Pradesh, India; CNS Pharmacology, Conscience Research, Pocket F-233, B, Dilshad Garden, Delhi 110095, India. Electronic address: drbhupeshresearch@gmail.com.
Jazyk: angličtina
Zdroj: Physiology & behavior [Physiol Behav] 2015 Dec 01; Vol. 152 (Pt A), pp. 182-93. Date of Electronic Publication: 2015 Sep 15.
DOI: 10.1016/j.physbeh.2015.09.007
Abstrakt: Vascular risk factors are associated with a higher incidence of dementia. Diabetes mellitus is considered as a main risk factor for Alzheimer's disease and vascular dementia. Both forms of dementia are posing greater risk to the world population and are increasing at a faster rate. In the past we have reported the induction of vascular dementia by experimental diabetes. This study investigates the role of vildagliptin, a dipeptidyl peptidase-4 inhibitor in the pharmacological interdiction of pancreatectomy diabetes induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. Pancreatectomy diabetes rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with increase in brain inflammation, oxidative stress and calcium. Administration of vildagliptin has significantly attenuated pancreatectomy induced impairment of learning, memory, endothelial function, blood brain barrier permeability and biochemical parameters. It may be concluded that vildagliptin, a dipeptidyl peptidase-4 inhibitor may be considered as potential pharmacological agents for the management of pancreatectomy induced endothelial dysfunction and subsequent vascular dementia. The selective modulators of dipeptidyl peptidase-4 may further be explored for their possible benefits in vascular dementia.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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