SAMP8 mice have altered hippocampal gene expression in long term potentiation, phosphatidylinositol signaling, and endocytosis pathways

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 whic...

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Bibliographic Details
Published in:Neurobiology of aging 2014, Vol.35 (1), p.159-168
Main Authors: Armbrecht, Harvey J, Siddiqui, Akbar M, Green, Michael, Farr, Susan A, Kumar, Vijaya B, Banks, William A, Patrick, Ping, Shah, Gul N, Morley, John E
Format: Article
Language:English
Subjects:
Aging - genetics
Aging - physiology
Amyloid beta-Peptides - metabolism
Animals
Clathrin-mediated endocytosis
Endocytosis - genetics
Endocytosis - physiology
Gene Expression
Gene Expression Regulation, Developmental - genetics
Gene Expression Regulation, Developmental - physiology
Hippocampal gene expression
Hippocampus - metabolism
Hippocampus - physiology
Internal Medicine
Learning - physiology
Long term potentiation
Long-Term Potentiation - genetics
Long-Term Potentiation - physiology
Memory - physiology
Memory Disorders - genetics
Memory loss
Mice
Mice, Inbred Strains
Neurology
Phosphatidylinositol signaling
Phosphatidylinositols - genetics
Phosphatidylinositols - physiology
SAMP8 mouse
Signal Transduction - genetics
Signal Transduction - physiology
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Summary: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.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2013.07.018