Please use this identifier to cite or link to this item: http://hdl.handle.net/10603/71499
Full metadata record
DC FieldValueLanguage
dc.coverage.spatialPHARMACOLOGY
dc.date.accessioned2016-01-25T12:15:28Z-
dc.date.available2016-01-25T12:15:28Z-
dc.identifier.urihttp://hdl.handle.net/10603/71499-
dc.description.abstractHypertension is a prevailing risk factor for cognitive impairment the most common cause of Vascular Dementia but a pathophysiological mechanistic link is still ambiguous Cyclic AMP is broken down by Camp specific phosphodiesterase that are expressed throughout the brain Inhibition of PDE4 leads to elevation of cAMP PKA pCREB in the hippocampus This signaling cascade is essential for establishing memory However there are no reports whether PDE4 inhibitors may improve the learning and memory dysfunction induced by HT The aim of the present study is to evaluate the feasibility of PDE4 inhibitors as a therapeutic agent for cognitive dysfunction induced by HT we examined the effects of rolipram and roflumilast on the impairment of learning and memory in hypertensive rats We used 2K1C and DOCA salt hypertensive models to induce learning and memory defects SBP was measured by tail cuff method Elevated plus maze and novel object recognition task models were used to evaluate the cognitive improvement Plasma and brain concentrations of rolipram roflumilast were studied after the behavioral task In addition mRNA expression of PDE4 subtypes ABCD and phosphorylation of CREB were also assessed in the hippocampus tissue SBP kidney weight and heart index were significantly increased in hypertensive rats when compared with their age matched sham operated rats There was no significant difference in SBP among the PDE4 treatment groups in both the models The retention latency on the second day in the elevated plus maze model was significantly shortened after repeated administration of rolipram or roflumilast Further PDE4 inhibitors significantly reversed time induced memory deficit in NORT Dose linear plasma and brain concentrations of rolipram and roflumilast were observed The PDE4B and PDE4D gene expression was significantly enhanced in hypertensive rats compared with sham operated however PDE4A and PDE4C remained unaltered Repeated dose treatment of PDE4 inhibitors caused down regulation of PDE4B and PDE4D leading to dose depen
dc.format.extent1-160
dc.languageEnglish
dc.relation102-126
dc.rightsuniversity
dc.titlePHOSPHODIESTERASE4 INHIBITORS AMELIORATE HYPERTENSION INDUCED COGNITIVE IMPAIRMENT OF LEARNING AND MEMORY FUNCTIONS via cAMP CREB SIGNALLING SYSTEM
dc.title.alternative
dc.creator.researcherSUGIN LAL JABARIS. S
dc.subject.keywordAMELIORATE HYPERTENSION
dc.subject.keywordCOGNITIVE IMPAIRMENT
dc.subject.keywordCREB SIGNALLING
dc.subject.keywordPHOSPHODIESTERASE4
dc.description.noteSUMMARY PAGES: 98-101 REFERENCE PAGES:102- 126 ANNEXURE PAGES : 129- 160
dc.contributor.guideSARAVANA BABU. C. Dr
dc.publisher.placeChennai
dc.publisher.universitySri Ramachandra University
dc.publisher.institutionCollege of Pharmacy
dc.date.registered02/01/2012
dc.date.completed08/01/2016
dc.date.awarded08/01/2016
dc.format.dimensionsA4
dc.format.accompanyingmaterialNone
dc.source.universityUniversity
dc.type.degreePh.D.
Appears in Departments:College of Pharmacy



Items in Shodhganga are protected by copyright, with all rights reserved, unless otherwise indicated.

Altmetric Badge: