Prior pathology in the basal forebrain cholinergic system predisposes to inflammation-induced working memory deficits: reconciling inflammatory and cholinergic hypotheses of delirium.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Robert H FieldColm Cunningham

Abstract

Delirium is a profound, acute confusional state that leads to long-term cognitive decline. Increased anticholinergic medications and prior dementia, in which basal forebrain cholinergic degeneration is a prominent feature, both predict delirium. Thus, cholinergic hypoactivity is thought to be important in cognitive dysfunction during delirium, and acute systemic inflammation is a major trigger for this dysfunction. Here, we hypothesize that decreased cholinergic function confers increased susceptibility to acute inflammation-induced cognitive deficits. We used the murine-p75-saporin immunotoxin (mu-p75-sap) to induce selective lesions of the basal forebrain cholinergic system in mice, mimicking early dementia-associated cholinergic loss, and superimposed systemic inflammation using low-dose bacterial lipopolysaccharide (LPS). Intracerebroventricular injection of mu-p75-sap produced depletion of cholinergic neurons in the basal forebrain and decreased innervation of the hippocampus, but left performance on hippocampal-dependent reference and working memory tasks relatively intact. However, systemic LPS (100 μg/kg) induced acute and transient working memory deficits in lesioned animals without effect in unlesioned controls. CNS i...Continue Reading

References

Jun 26, 2004·The European Journal of Neuroscience·Christopher L HunterAnn-Charlotte Granholm
Oct 7, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Colm CunninghamV Hugh Perry
Mar 17, 2006·The New England Journal of Medicine·Sharon K Inouye
Feb 3, 2007·The Journal of Clinical Investigation·Kevin J Tracey

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Citations

Apr 20, 2013·Rejuvenation Research·Sophia E de Rooij, Barbara C van Munster
Oct 3, 2013·Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society·Karin J Neufeld, Christine Thomas
May 31, 2013·Annals of Intensive Care·Romain SonnevilleTarek Sharshar
Sep 27, 2013·Age and Ageing·Alasdair M J MaclullichColm Cunningham
Feb 1, 2014·Critical Care : the Official Journal of the Critical Care Forum·Valerie J Page, Annalisa Casarin
Apr 10, 2014·Clinical Medicine : Journal of the Royal College of Physicians of London·Barbara C van Munster, S E de Rooij
Feb 28, 2015·Military Medical Research·Qing-Hong ZhangYong-Ming Yao
Jun 4, 2014·International Journal of Molecular Sciences·Miroslav Pohanka
Nov 12, 2013·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·José R Maldonado
Jan 5, 2014·Journal of the American Geriatrics Society·Leiv Otto WatneTorgeir B Wyller
May 11, 2015·Journal of Neurology·Emma R L C VardyAlison J Yarnall
Oct 7, 2015·Frontiers in Cellular Neuroscience·Quan RenZhongcong Xie
Sep 23, 2014·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·Daniel H J DavisColm Cunningham
Jul 4, 2015·Lancet Neurology·Tamara G FongSharon K Inouye
Sep 9, 2015·Frontiers in Medicine·Adonis SferaCarolina Osorio
Jun 25, 2015·Frontiers in Aging Neuroscience·Ganna AndrosovaReinhard Schneider
May 27, 2014·Journal of Neurology, Neurosurgery, and Psychiatry·Rachel L GoreJohn T O'Brien
Aug 14, 2012·Brain, Behavior, and Immunity·Colm Cunningham, Alasdair M J Maclullich
Jun 7, 2014·Frontiers in Psychiatry·Adonis Sfera, Carolina Osorio
May 29, 2016·Journal of Neuroimmunology·Roua AbulkassimTrevor J Bushell
Jun 2, 2016·International Psychogeriatrics·Martin G Cole, Jane Mccusker
Jun 29, 2016·Acta Clinica Belgica·Charalampos PierrakosDavid De Bels
May 26, 2016·Hospital Practice·Vicente Cés Souza-DantasJorge Salluh
Sep 30, 2016·Pharmacological Reviews·Fulton T CrewsDonita L Robinson
Apr 11, 2017·International Journal of Geriatric Psychiatry·Zoë TiegesAlasdair M J MacLullich
Dec 12, 2013·Journal of Pharmacy Practice·Julie KalabalikRadwa El-Srougy
Mar 17, 2018·Neurology India·Levente MolnárCsilla Molnár
Nov 24, 2017·Frontiers in Medicine·Giuseppe BellelliMatteo Cesari
May 16, 2018·Critical Care Medicine·Rakesh C Arora, Colm Cunningham
Mar 12, 2019·Journal of Geriatric Psychiatry and Neurology·Monique MichelsFelipe Dal-Pizzol
Apr 19, 2013·Biomedical Research·Yutaka Masuda, Toshihiro Sugiyama
Aug 15, 2019·Brain : a Journal of Neurology·Seán O'DowdJohn-Paul Taylor
Feb 6, 2018·European Psychiatry : the Journal of the Association of European Psychiatrists·G WintererUNKNOWN BioCog consortium

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