Research article summary (published 30 Dec 2007):

Long-term potentiation inhibition by low-level N-methyl-D-aspartate receptor activation involves calcineurin, nitric oxide, and p38 mitogen-activated protein kinase.

Full Abstract

Low-level activation of N-methyl-d-aspartate receptors (NMDARs) results in a decrease in the ability of tetanic stimulation to induce long-term potentiation (LTP). This NMDAR-mediated LTP inhibition is observed with low micromolar concentrations of NMDA or chelation of ambient extracellular zinc. In rat hippocampal slices, we examined whether LTP inhibition by 1 muM NMDA and zinc chelation share common mechanisms. We found that both forms of LTP inhibition involve nitric oxide (NO) synthase (NOS) and calcineurin. Furthermore, both forms of LTP inhibition are overcome by block of p38 mitogen-activated protein kinase (MAPK), but not by inhibition of extracellular signal-regulated kinase 1/2 or c-Jun-N-terminal kinase. A p38 antagonist also overcame the block of LTP by sodium nitroprusside, an agent that releases NO, suggesting that NO release occurs upstream of MAPK activation. Despite the involvement of p38 MAPK in NMDAR-mediated LTP inhibition, p38 antagonism did not enhance LTP induction in response to weak tetanic stimulation under baseline conditions. These results indicate that p38 MAPK is part of a complex NMDAR-driven signaling pathway involving calcineurin and NO that helps to regulate synaptic plasticity in the CA1 region. (c) 2007 Wiley-Liss, Inc.

Author information

Author/s: Izumi, Yukitoshi (Y); Tokuda, Kazuhiro (K); Zorumski, Charles F (CF);

Affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Grants: AA12951 (Agency:NIAAA NIH HHS) ; AG18434 (Agency:NIA NIH HHS) ; MH45493 (Agency:NIMH NIH HHS) ; MH77791 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Hippocampus (Hippocampus), published in United States. (Language: eng)

Reference: 2008-; vol 18 (issue 3) : pp 258-65

Dates: Created 2008/02/27; Completed 2008/03/27; Revised 2008/11/21;

PMID: 18000819, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Calcineurin - metabolism Chelating Agents - pharmacology Enzyme Inhibitors - pharmacology Excitatory Amino Acid Agonists - pharmacology Hippocampus - drug effects; metabolism Long-Term Potentiation - drug effects; physiology N-Methylaspartate - pharmacology Neural Inhibition - drug effects; physiology Neuronal Plasticity - drug effects; physiology

Neuronal Plasticity - drug effects; physiology Nitric Oxide - metabolism Nitric Oxide Donors - pharmacology Nitric Oxide Synthase - metabolism Organ Culture Techniques Rats Receptors, N-Methyl-D-Aspartate - drug effects; metabolism Signal Transduction - drug effects; physiology Zinc - metabolism p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; metabolism

Associated Chemicals: Chelating Agents (0) ; Enzyme Inhibitors (0) ; Excitatory Amino Acid Agonists (0) ; Nitric Oxide Donors (0) ; Receptors, N-Methyl-D-Aspartate (0) ; Nitric Oxide (10102-43-9) ; N-Methylaspartate (6384-92-5) ; Zinc (7440-66-6) ; Nitric Oxide Synthase (EC 1.14.13.39) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.1.37) ; Calcineurin (EC 3.1.3.16)

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