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Symposium on disorders of memory
011 Exploring animal models of delirium during dementia
  1. C Cunningham

    Author information: Colm Cunningham Trinity College Institute of Neuroscience, TCD, Dublin 2, Rep of Ireland (colm.cunningham{at}tcd). That is, my main research interests are in neurodegeneration and in brain inflammation. As a research fellow/research lecturer in Trinity College Dublin, my primary interest up until this point has been research. However, I have spent the last 8 years designing and supervising undergraduate research projects in the laboratory. I take this responsibility very seriously and a number of the students I supervised have proceeded to Ph.D. studies and two have had publications based on work conducted in these projects. I currently supervise one PhD student and co-supervise second, as well as supervising students on the Neuroscience MSc and the HRB 4 year Neuroscience PhD programme. I currently design and deliver 2 lecture courses: Neuroinflammation and experimental neuropathology to Senior Sophister Neuroscience students and Therapeutic approaches in neurodegenerative disease to Molecular Medicine Senior Sophisters. I have also lectured to medical students, during my time in Southampton, on the immune-privileged status of the brain.

Abstract

Abstract: Delirium is an acute, severe neuropsychiatric syndrome, characterised by cognitive deficits. It is highly prevalent in ageing and dementia and is frequently precipitated by peripheral infections. Delirium is poorly understood and the lack of biologically relevant animal models has limited basic research. We proposed that prior pathology and superimposed systemic inflammation would combine to produce acute impairments relevant to delirium during dementia. Using chronic neurodegeneration induced during prion disease or selective lesioning of the basal forebrain cholinergic nuclei we have developed animal models to address this hypothesis. Normal mice or animals with these prior pathologies were challenged systemically with bacterial endotoxin (lipopolysaccharide (LPS) 100 μg/kg) and assessed on working memory tasks dependent on the brain region showing prior pathology. LPS had no effect on working memory in normal animals but induced significant acute and reversible working memory deficits in animals with either early synaptic loss, or limited basal forebrain lesions. Animals with prior pathology did not show deficits on these tasks in the absence of LPS. The deficits were associated with heightened CNS inflammatory responses to systemic inflammatory stimuli, despite equivalent systemic responses. Prior pathology, including microglial priming, synaptic loss and neuronal death predispose individuals to heightened cognitive deficits upon systemic inflammatory insults. The relevance of these findings for delirium during dementia will be discussed.

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