eCite Digital Repository

Knockout of amyloid β protein precursor (APP) expression alters synaptogenesis, neurite branching and axonal morphology of hippocampal neurons

Citation

Southam, KA and Stennard, F and Pavez, C and Small, DH, Knockout of amyloid β protein precursor (APP) expression alters synaptogenesis, neurite branching and axonal morphology of hippocampal neurons, Neurochemical Research pp. 1-10. ISSN 0364-3190 (2018) [Refereed Article]

Copyright Statement

Copyright 2018 Springer Science+Business Media, LLC

DOI: doi:10.1007/s11064-018-2512-0

Abstract

The function of the β-A4 amyloid protein precursor (APP) of Alzheimer's disease (AD) remains unclear. APP has a number of putative roles in neuronal differentiation, survival, synaptogenesis and cell adhesion. In this study, we examined the development of axons, dendrites and synapses in cultures of hippocampus neutrons derived from APP knockout (KO) mice. We report that loss of APP function reduces the branching of cultured hippocampal neurons, resulting in reduced synapse formation. Using a compartmentalised culture approach, we found reduced axonal outgrowth in cultured hippocampal neurons and we also identified abnormal growth characteristics of isolated hippocampal neuron axons. Although APP has previously been suggested to play an important role in promoting cell adhesion, we surprisingly found that APPKO hippocampal neurons adhered more strongly to a poly-L-lysine substrate and their neurites displayed an increased density of focal adhesion puncta. The findings suggest that the function of APP has an important role in both dendritic and axonal growth and that endogenous APP may regulate substrate adhesion of hippocampal neurons. The results may explain neuronal and synaptic morphological abnormalities in APPKO mice and the presence of abnormal APP expression in dystrophic neurites around amyloid deposits in AD.

Item Details

Item Type:Refereed Article
Keywords:APP, alzheimer’s disease, amyloid, axon pathfinding, neurite outgrowth
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Southam, KA (Dr Katherine Southam)
Author:Stennard, F (Dr Fiona Stennard)
Author:Pavez, C (Miss Cassandra Pavez)
Author:Small, DH (Professor David Small)
ID Code:125484
Year Published:2018
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-04-19
Last Modified:2018-05-02
Downloads:0

Repository Staff Only: item control page