title: Neuroprotective effect of selective DPP-4 inhibitor in experimental vascular dementia.
abstract: 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.
authors.affiliation: 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.
authors.forename: Swati
authors.initials: S
authors.lastname: Jain
authors.affiliation: 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.
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Sharma
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001288:Attention / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D056344:Executive Function / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology*; D010180:Pancreatectomy; D011759:Pyrrolidines / Q000494:pharmacology*; D017208:Rats, Wistar; D016896:Treatment Outcome; D000077597:Vildagliptin
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D018696:Neuroprotective Agents; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin; D000218:Adamantane
keywords: Attentional-set shifting; Blood brain barrier; DPP-4 inhibitor; Morris water maze; Oxidative stress