Region-Specific Differences in Amyloid Precursor Protein Expression in the Mouse Hippocampus

Domenico Del Turco,Jessica Schlaudraff,Kristina Endres,Thomas Deller,Meike Hick,Mandy H Paul,Ulrike C Müller

doi:10.3389/fnmol.2016.00134

Abstract

The physiological role of amyloid precursor protein (APP) has been extensively investigated in the rodent hippocampus. Evidence suggests that APP plays a role in synaptic plasticity, dendritic and spine morphogenesis, neuroprotection and—at the behavioral level—hippocampus-dependent forms of learning and memory. Intriguingly, however, studies focusing on the role of APP in synaptic plasticity have reported diverging results and considerable differences in effect size between the dentate gyrus (DG) and area CA1 of the mouse hippocampus. We speculated that regional differences in APP expression could underlie these discrepancies and studied the expression of APP in both regions using immunostaining, in situ hybridization (ISH), and laser microdissection (LMD) in combination with quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting. In sum, our results show that APP is approximately 1.7-fold higher expressed in pyramidal cells of Ammon’s horn than in granule cells of the DG. This regional difference in APP expression may explain why loss-of-function approaches using APP-deficient mice revealed a role for APP in Hebbian plasticity in area CA1, whereas this could not be shown in the DG of the same APP mutants.

Highlights

Amyloid precursor protein (APP) is an integral membrane protein involved in the pathogenesis of Alzheimer’s disease (AD)
We analyzed the expression of amyloid precursor protein (APP) at the protein and mRNA level in the gcl and CA1 pcl of the adult mouse hippocampus using confocal immunofluorescence, in situ hybridization (ISH) and laser microdissection (LMD) in combination with quantitative polymerase chain reaction (qPCR) or western blot analysis
APP expression is ∼1.7× stronger at both mRNA and protein level in CA1 pyramidal cells compared to dentate granule cells

Summary

Introduction

Amyloid precursor protein (APP) is an integral membrane protein involved in the pathogenesis of Alzheimer’s disease (AD). Proteolysis of APP by α-secretases (e.g., Postina et al, 2004; Yang et al, 2006; Fahrenholz, 2007; Prinzen et al, 2009; Saftig and Reiss, 2011; Kuhn et al, 2016), generates soluble APP-α (sAPPα), which is neuroprotective and important for neuronal plasticity (Turner et al, 2003; Ring et al, 2007; Aydin et al, 2012; Kögel et al, 2012) In the latter case, the Aß-peptide is not formed because α-secretases cleave APP within the Aß region of the protein.

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