HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 92/5/2853    most recent 00485.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (23) Citing Articles via Google Scholar Google Scholar Articles by Zhao, D. Articles by Xie, C.-W. Search for Related Content PubMed PubMed Citation Articles by Zhao, D. Articles by Xie, C.-W.

Amyloid Prevents Activation of Calcium/Calmodulin-Dependent Protein Kinase II and AMPA Receptor Phosphorylation During Hippocampal Long-Term Potentiation

Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine and Neuropsychiatric Institute, University of California, Los Angeles, California 90024

Submitted 9 May 2004; accepted in final form 10 June 2004

Accumulation of amyloid -peptides (A) in the brain has been linked with memory loss in Alzheimer's disease and its animal models. However, the synaptic mechanism by which A causes memory deficits remains unclear. We previously showed that acute application of A inhibited long-term potentiation (LTP) in the hippocampal perforant path via activation of calcineurin, a Ca²⁺-dependent protein phosphatase. This study examined whether A could also inhibit Ca²⁺/calmodulin dependent protein kinase II (CaMKII), further disrupting the dynamic balance between protein kinase and phosphatase during synaptic plasticity. Immunoblot analysis was conducted to measure autophosphorylation of CaMKII at Thr²⁸⁶ and phosphorylation of the GluR1 subunit of AMPA receptors in single rat hippocampal slices. A high-frequency tetanus applied to the perforant path significantly increased CaMKII autophosphorylation and subsequent phosphorylation of GluR1 at Ser⁸³¹, a CaMKII-dependent site, in the dentate area. Acute application of A_1–42 inhibited dentate LTP and associated phosphorylation processes, but was without effect on phosphorylation of GluR1 at Ser⁸⁴⁵, a protein kinase A-dependent site. These results suggest that activity-dependent CaMKII autophosphorylation and AMPA receptor phosphorylation are essential for dentate LTP. Disruption of such mechanisms could directly contribute to A-induced deficits in hippocampal synaptic plasticity and memory.

This article has been cited by other articles:

				N. Origlia, M. Righi, S. Capsoni, A. Cattaneo, F. Fang, D. M. Stern, J. X. Chen, A. M. Schmidt, O. Arancio, S. D. Yan, et al. Receptor for Advanced Glycation End Product-Dependent Activation of p38 Mitogen-Activated Protein Kinase Contributes to Amyloid-{beta}-Mediated Cortical Synaptic Dysfunction J. Neurosci., March 26, 2008; 28(13): 3521 - 3530. [Abstract] [Full Text] [PDF]

				M. Townsend, T. Mehta, and D. J. Selkoe Soluble Abeta Inhibits Specific Signal Transduction Cascades Common to the Insulin Receptor Pathway J. Biol. Chem., November 16, 2007; 282(46): 33305 - 33312. [Abstract] [Full Text] [PDF]

				J. S. Jacobsen, C.-C. Wu, J. M. Redwine, T. A. Comery, R. Arias, M. Bowlby, R. Martone, J. H. Morrison, M. N. Pangalos, P. H. Reinhart, et al. Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease PNAS, March 28, 2006; 103(13): 5161 - 5166. [Abstract] [Full Text] [PDF]

				C. L. Palmer, L. Cotton, and J. M. Henley The Molecular Pharmacology and Cell Biology of {alpha}-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors Pharmacol. Rev., June 1, 2005; 57(2): 253 - 277. [Abstract] [Full Text] [PDF]