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Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Borovok, Natalia Nesher, Elimelech Levin, Yishai Reichenstein, Michal Pinhasov, Albert Michaelevski, Izhak
Description	Author Affiliation: Borovok N ( From the Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel-Aviv 6997801, Israel); Nesher E ( §Department of Molecular Biology, Ariel University, Ariel 4070000, Israel); Levin Y ( ¶de Botton Institute for Protein Profiling, The Nancy & Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 7610001, Israel); Reichenstein M ( From the Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel-Aviv 6997801, Israel); Pinhasov A ( §Department of Molecular Biology, Ariel University, Ariel 4070000, Israel); Michaelevski I ( From the Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel-Aviv 6997801, Israel)
Abstract	Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein trafficking, enhancement of metabolic activity, and Wnt signaling pathway during the steep phase of memory formation; and (3) cytoskeleton organization proteins. Taken together, this study clearly demonstrates dynamic assembly and disassembly of protein-protein interaction networks depending on the stage of memory formation engrams.
File Format	HTM / HTML
ISSN	15359476
e-ISSN	15359484
Journal	Molecular & Cellular Proteomics
Issue Number	2
Volume Number	15
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2016-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Proteomics Aging Genetics Hippocampus Metabolism Neuronal Plasticity Proteomics Synapses Pathology Animals Gene Expression Regulation Physiopathology Maze Learning Memory, Long-term Physiology Mice Protein Biosynthesis Spatial Memory Synaptic Transmission Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Medicine Analytical Chemistry Molecular Biology Biochemistry

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