Dataset Information

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

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.

SUBMITTER: Del Turco D

PROVIDER: S-EPMC5126089 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Del Turco Domenico D Paul Mandy H MH Schlaudraff Jessica J Hick Meike M Endres Kristina K Müller Ulrike C UC Deller Thomas T

Frontiers in molecular neuroscience 20161129

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 (D ...[more]

PMID: 27965537

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Project description:BackgroundDifferential processing of the amyloid precursor protein liberates either amyloid-ß, a causative agent of Alzheimer's disease, or secreted amyloid precursor protein-alpha (sAPP?), which promotes neuroprotection, neurotrophism, neurogenesis and synaptic plasticity. The underlying molecular mechanisms recruited by sAPP? that underpin these considerable cellular effects are not well elucidated. As these effects are enduring, we hypothesised that regulation of gene expression may be of importance and examined temporally specific gene networks and pathways induced by sAPP? in rat hippocampal organotypic slice cultures. Slices were exposed to 1 nM sAPP? or phosphate buffered saline for 15 min, 2 h or 24 h and sAPP?-associated gene expression profiles were produced for each time-point using Affymetrix Rat Gene 1.0 ST arrays (moderated t-test using Limma: p?<?0.05, and fold change?±?1.15).ResultsTreatment of organotypic hippocampal slice cultures with 1 nM sAPP? induced temporally distinct gene expression profiles, including mRNA and microRNA associated with Alzheimer's disease. Having demonstrated that treatment with human recombinant sAPP? was protective against N-methyl d-aspartate-induced toxicity, we next explored the sAPP?-induced gene expression profiles. Ingenuity Pathway Analysis predicted that short-term exposure to sAPP? elicited a multi-level transcriptional response, including upregulation of immediate early gene transcription factors (AP-1, Egr1), modulation of the chromatin environment, and apparent activation of the constitutive transcription factors CREB and NF-?B. Importantly, dynamic regulation of NF-?B appears to be integral to the transcriptional response across all time-points. In contrast, medium and long exposure to sAPP? resulted in an overall downregulation of gene expression. While these results suggest commonality between sAPP? and our previously reported analysis of plasticity-related gene expression, we found little crossover between these datasets. The gene networks formed following medium and long exposure to sAPP? were associated with inflammatory response, apoptosis, neurogenesis and cell survival; functions likely to be the basis of the neuroprotective effects of sAPP?.ConclusionsOur results demonstrate that sAPP? rapidly and persistently regulates gene expression in rat hippocampus. This regulation is multi-level, temporally specific and is likely to underpin the neuroprotective effects of sAPP?.

Dataset Information

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

Publications

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

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