title: Characterisation of the effect of knockout of the amyloid precursor protein on outcome following mild traumatic brain injury.
abstract: The amyloid precursor protein (APP) increases following traumatic brain injury (TBI), although the functional significance of this remains unclear largely because the functions of the subsequent APP metabolites are so different: Aβ is neurotoxic whilst sAPPα is neuroprotective. To investigate this further, APP wildtype and knockout mice were subjected to mild diffuse TBI and their outcomes compared. APP knockout mice displayed significantly worse cognitive and motor deficits, as demonstrated by the Barnes Maze and rotarod respectively, than APP wildtype mice. This was associated with a significant increase in hippocampal and cortical cell loss, as well as axonal injury, in APP knockout mice and an impaired neuroreparative response as indicated by diminished GAP-43 immunoreactivity when compared to APP wildtype mice. This study is the first to demonstrate that endogenous APP is beneficial following mild TBI, suggesting that the upregulation of APP observed following injury is an acute protective response.
authors.affiliation: Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide SA, Australia.
authors.forename: Frances
authors.initials: F
authors.lastname: Corrigan
authors.forename: Robert
authors.initials: R
authors.lastname: Vink
authors.forename: Peter C
authors.initials: PC
authors.lastname: Blumbergs
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Roberto
authors.initials: R
authors.lastname: Cappai
authors.forename: Corinna
authors.initials: C
authors.lastname: van den Heuvel
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020127:Recovery of Function / Q000502:physiology*; D045442:Rotarod Performance Test
chemical_list: D016564:Amyloid beta-Protein Precursor; D053148:Caspase 3