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Type: Journal article
Title: SAMP8 mice have altered hippocampal gene expression in long term potentiation, phosphatidylinositol signaling, and endocytosis pathways
Author: Armbrecht, H.
Siddiqui, A.
Green, M.
Farr, S.
Kumar, V.
Banks, W.
Patrick, P.
Shah, G.
Morley, J.
Citation: Neurobiology of Aging, 2014; 35(1):159-168
Publisher: Elsevier
Issue Date: 2014
ISSN: 0197-4580
Statement of
Harvey J. Armbrecht, Akbar M. Siddiqui, Michael Green, Susan A. Farr, Vijaya B. Kumar, William A. Banks, Ping Patrick, Gul N. Shah, John E. Morley
Abstract: The senescence-accelerated mouse (SAMP8) strain exhibits decreased learning and memory and increased amyloid beta (Aβ) peptide accumulation at 12 months. To detect differences in gene expression in SAMP8 mice, we used a control mouse that was a 50% cross between SAMP8 and CD-1 mice and which showed no memory deficits (50% SAMs). We then compared gene expression in the hippocampus of 4- and 12-month-old SAMP8 and control mice using Affymetrix gene arrays. At 12 months, but not at 4 months, pathway analysis revealed significant differences in the long term potentiation (6 genes), phosphatidylinositol signaling (6 genes), and endocytosis (10 genes) pathways. The changes in long term potentiation included mitogen-activated protein kinase (MAPK) signaling (N-ras, cAMP responsive element binding protein [CREB], protein phosphatase inhibitor 1) and Ca-dependent signaling (inositol triphosphate [ITP] receptors 1 and 2 and phospholipase C). Changes in phosphatidylinositol signaling genes suggested altered signaling through phosphatidylinositol-3-kinase, and Western blotting revealed phosphorylation changes in serine/threonine protein kinase AKT and 70S6K. Changes in the endocytosis pathway involved genes related to clathrin-mediated endocytosis (dynamin and clathrin). Endocytosis is required for receptor recycling, is involved in Aβ metabolism, and is regulated by phosphatidylinositol signaling. In summary, these studies demonstrate altered gene expression in 3 SAMP8 hippocampal pathways associated with memory formation and consolidation. These pathways might provide new therapeutic targets in addition to targeting Aβ metabolism itself.
Keywords: SAMP8 mouse; Hippocampal gene expression; Memory loss; Long term potentiation; Phosphatidylinositol signaling; Clathrin-mediated endocytosis
Rights: © 2014 Elsevier
RMID: 0030016253
DOI: 10.1016/j.neurobiolaging.2013.07.018
Appears in Collections:Medicine publications

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