Senechal, Yann, Prut, Laetitia, Kelly, Peter, Staufenbiel, Matthias, Natt, Francois, Hoyer, Daniel, Wiessner, Christoph and Dev, Kumlesh K. (2008) Increased exploratory activity of APP23 mice in a novel environment is reversed by siRNA. Brain Research, 1243. pp. 124-133. ISSN 1872-6240

Abstract

Genetic abnormalities in amyloid precursor protein (APP) are associated with Down's syndrome and familial Alzheimer's disease where hallmark plaques contain A beta peptides derived from APP. Both APP and its derivatives are implicated in neurodegenerative processes and may play important physiological and pathophysiological roles in synaptic function. Here, we show that young APP23 transgenic mice overexpressing human APP with the Swedish double mutation display altered novelty seeking behavior before the age of plaque onset. Using short interfering RNA (siRNA) targeted against APP, we investigate the direct contribution of APP and its derivatives to this behavioral deficit. After validating siRNAs targeting human APP in vitro, siRNAs were infused directly into the brain of APP23 mice for 2 weeks. Behavioral analysis shows that infusion of siRNA targeted against APP completely reverses increased exploratory activity in APP23 mice. Collectively, these data suggest that excessive APP and/or its derivatives, causes a hyperactive phenotype in APP23 mice when placed in a novel environment, which is fully reversible and not linked to plaque deposits.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Amyloid precursor protein (APP); Alzheimer's disease (AD); Short interfering RNA (siRNA); Knockdown; APP23 mouse; Locomotor behaviour
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Date Deposited:	14 Dec 2009 13:48
Last Modified:	31 Jan 2013 00:55
URI:	https://oak.novartis.com/id/eprint/1382