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dc.contributor.authorCulley, Deborah J.en_US
dc.contributor.authorSnayd, Maryen_US
dc.contributor.authorBaxter, Mark G.en_US
dc.contributor.authorXie, Zhongcongen_US
dc.contributor.authorLee, In Hoen_US
dc.contributor.authorRudolph, Jamesen_US
dc.contributor.authorInouye, Sharon K.en_US
dc.contributor.authorMarcantonio, Edward R.en_US
dc.contributor.authorCrosby, Gregoryen_US
dc.date.accessioned2014-07-07T17:03:13Z
dc.date.issued2014en_US
dc.identifier.citationCulley, Deborah J., Mary Snayd, Mark G. Baxter, Zhongcong Xie, In Ho Lee, James Rudolph, Sharon K. Inouye, Edward R. Marcantonio, and Gregory Crosby. 2014. “Systemic Inflammation Impairs Attention and Cognitive Flexibility but Not Associative Learning in Aged Rats: Possible Implications for Delirium.” Frontiers in Aging Neuroscience 6 (1): 107. doi:10.3389/fnagi.2014.00107. http://dx.doi.org/10.3389/fnagi.2014.00107.en
dc.identifier.issn1663-4365en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12406666
dc.description.abstractDelirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that systemic inflammation impairs prefrontal cortex function by assessing attention and executive function in aged animals. Aged (24-month-old) Fischer-344 rats received a single intraperitoneal injection of lipopolysaccharide (LPS; 50 μg/kg) or saline and were tested on the attentional set-shifting task (AST), an index of integrity of the prefrontal cortex, on days 1–3 post-injection. Plasma and frontal cortex concentrations of the cytokine TNFα and the chemokine CCL2 were measured by ELISA in separate groups of identically treated, age-matched rats. LPS selectively impaired reversal learning and attentional shifts without affecting discrimination learning in the AST, indicating a deficit in attention and cognitive flexibility but not learning globally. LPS increased plasma TNFα and CCL2 acutely but this resolved within 24–48 h. TNFα in the frontal cortex did not change whereas CCL2 increased nearly threefold 2 h after LPS but normalized by the time behavioral testing started 24 h later. Together, our data indicate that systemic inflammation selectively impairs attention and executive function in aged rodents and that the cognitive deficit is independent of concurrent changes in frontal cortical TNFα and CCL2. Because inattention is a prominent feature of clinical delirium, our data support a role for inflammation in the pathogenesis of this clinical syndrome and suggest this animal model could be useful for studying that relationship further.en
dc.language.isoen_USen
dc.publisherFrontiers Media S.A.en
dc.relation.isversionofdoi:10.3389/fnagi.2014.00107en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050637/pdf/en
dash.licenseLAAen_US
dc.subjectaging neuroscienceen
dc.subjectratsen
dc.subjectinflammationen
dc.subjectfrontal cortexen
dc.subjectlipopolysaccharidesen
dc.subjectCCL2en
dc.subjectset-shiftingen
dc.titleSystemic Inflammation Impairs Attention and Cognitive Flexibility but Not Associative Learning in Aged Rats: Possible Implications for Deliriumen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalFrontiers in Aging Neuroscienceen
dash.depositing.authorCulley, Deborah J.en_US
dc.date.available2014-07-07T17:03:13Z
dc.identifier.doi10.3389/fnagi.2014.00107*
dash.contributor.affiliatedRudolph, James
dash.contributor.affiliatedMarcantonio, Edward
dash.contributor.affiliatedXie, Zhongcong
dash.contributor.affiliatedCulley, Deborah
dash.contributor.affiliatedCrosby, Gregory
dash.contributor.affiliatedInouye, Sharon


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