title: Forebrain neurone-specific deletion of insulin-regulated aminopeptidase causes age related deficits in memory.
abstract: Central infusion of Insulin-Regulated Aminopeptidase (IRAP) inhibitors improves memory in both normal rodents and in models of memory deficit. However, in contrast, the global IRAP knockout mice (KO) demonstrate age-accelerated spatial memory deficits and no improvements in performance in any memory tasks. Potentially, the observed memory deficit could be due to the absence of IRAP in the developing brain. We therefore generated a postnatal forebrain neuron-specific IRAP knockout mouse line (CamKIIalphaCre; IRAPlox/lox). Unexpectedly, we demonstrated that postnatal deletion of IRAP in the brain results in significant deficits in both spatial reference and object recognition memory at three months of age, although spatial working memory remained intact. These results indicate a significant role for IRAP in postnatal brain development and normal function of the hippocampus in adulthood.
authors.affiliation: Florey Neuroscience Institutes and Centre for Neuroscience, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Holly R
authors.initials: HR
authors.lastname: Yeatman
authors.affiliation: College of Health and Biomedicine, VU St Albans, Victoria 3021, Australia.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Albiston
authors.affiliation: Department of Physiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Peta
authors.initials: P
authors.lastname: Burns
authors.affiliation: Department of Physiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia. Electronic address: siew.chai@monash.edu.
authors.forename: Siew Yeen
authors.initials: SY
authors.lastname: Chai
mesh_terms: D000367:Age Factors; D000818:Animals; D010122:Cystinyl Aminopeptidase / Q000172:deficiency / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008569:Memory Disorders / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D021641:Recognition, Psychology / Q000502:physiology*; D065852:Spatial Memory / Q000502:physiology*
chemical_list: D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase
keywords: Aminopeptidase; Angiotensin IV; Forebrain; IRAP; Memory