Linked Life Data

21036186

Source:http://linkedlifedata.com/resource/pubmed/id/21036186

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-6-20
pubmed:abstractText
Epidemiological studies estimate that greater than 60% of the adult US population may be categorized as either overweight or obese and there is a growing appreciation that obesity affects the functional integrity of the central nervous system (CNS). We recently developed a lentivirus (LV) vector that produces an insulin receptor (IR) antisense RNA sequence (IRAS) that when injected into the hypothalamus selectively decreases IR signaling in hypothalamus, resulting in increased body weight, peripheral adiposity and plasma leptin levels. To test the hypothesis that this obesity/hyperleptinemic phenotype would impair hippocampal synaptic transmission, we examined short term potentiation (STP) and long term potentiation (LTP) in the hippocampus of rats that received the LV-IRAS construct or the LV-Control construct in the hypothalamus (hypo-IRAS and hypo-Con, respectively). Stimulation of the Schaffer collaterals elicits STP that develops into LTP in the CA1 region of hypo-Con rats; conversely, hypo-IRAS rats exhibit STP that fails to develop into LTP. To more closely examine the potential role of hyperleptinemia in these electrophysiological deficits, hypo-IRAS were subjected to mild food restriction paradigms that would either: 1) prevent the development of the obesity phenotype; or 2) reverse an established obesity phenotype in hypo-IRAS rats. Both of these paradigms restored LTP in the CA1 region and reversed the decreases in the phosphorylated/total ratio of GluA1 Ser845 AMPA receptor subunit expression observed in the hippocampus of hypo-IRAS rats. Collectively, these data support the hypothesis that obesity impairs hippocampal synaptic transmission and support the hypothesis that these deficits are mediated through the impairment of hippocampal leptin activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1873-507X
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
235-41
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21036186-Adiposity, pubmed-meshheading:21036186-Animals, pubmed-meshheading:21036186-Area Under Curve, pubmed-meshheading:21036186-Autoradiography, pubmed-meshheading:21036186-Body Weight, pubmed-meshheading:21036186-Corticosterone, pubmed-meshheading:21036186-Disease Models, Animal, pubmed-meshheading:21036186-Down-Regulation, pubmed-meshheading:21036186-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:21036186-Food Deprivation, pubmed-meshheading:21036186-Hippocampus, pubmed-meshheading:21036186-Hypothalamus, pubmed-meshheading:21036186-Insulin, pubmed-meshheading:21036186-Leptin, pubmed-meshheading:21036186-Long-Term Potentiation, pubmed-meshheading:21036186-Male, pubmed-meshheading:21036186-Obesity, pubmed-meshheading:21036186-Phosphorylation, pubmed-meshheading:21036186-RNA, Antisense, pubmed-meshheading:21036186-Rats, pubmed-meshheading:21036186-Rats, Sprague-Dawley, pubmed-meshheading:21036186-Receptor, Insulin, pubmed-meshheading:21036186-Receptors, AMPA, pubmed-meshheading:21036186-Serine
pubmed:year
2011
pubmed:articleTitle
Obesity/hyperleptinemic phenotype adversely affects hippocampal plasticity: effects of dietary restriction.
pubmed:affiliation
Department of Pharmacology, Physiology and Neuroscience, School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural