Hippocampal spine-associated Rap-specific GTPase-activating protein induces enhancement of learning and memory in postnatally hypoxia-exposed mice

Abstract Spine-associated Rap-specific GTPase-activating protein (SPAR) is a postsynaptic protein that forms a complex with postsynaptic density (PSD)-95 and N -methyl- d -aspartate receptors (NMDARs), and morphologically regulates dendritic spines. Mild intermittent hypoxia (IH, 16.0% O2 , 4 h/day...

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Published in:	Neuroscience Vol. 162; no. 2; pp. 404 - 414
Main Authors:	Lu, X.-J, Chen, X.-Q, Weng, J, Zhang, H.-Y, Pak, D.T, Luo, J.-H, Du, J.-Z
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Ltd 18-08-2009 Elsevier
Subjects:	Animals Animals, Newborn Biological and medical sciences Female Fundamental and applied biological sciences. Psychology Gene Knockdown Techniques GTPase-Activating Proteins - biosynthesis GTPase-Activating Proteins - genetics Hippocampus - metabolism Hippocampus - physiopathology hypoxia Hypoxia - physiopathology Learning learning and memory Long-Term Potentiation LTP Male Maze Learning Memory Mice Mice, Inbred ICR Neurology Oligonucleotides, Antisense - pharmacology postnatal SPAR Spatial Behavior Vertebrates: nervous system and sense organs postnatal spine-associated Rap-specific GTPase-activating protein RT room temperature L-LTP fEPSPs PPF LTP high frequency stimulation analysis of variance HFS ANOVA postnatal day late phase long-term potentiation IH P (with number) PSD postsynaptic density hypoxia E-LTP field excitatory postsynaptic potentials SPAR ACSF early-phase long-term potentiation intermittent hypoxia N-methyl- d-aspartate receptor artificial cerebrospinal fluid NR2B learning and memory NMDAR N-methyl- d-aspartate receptor subunit 2B paired-pulse facilitation long-term potentiation Oxygen Enzyme Triphosphoric monoester hydrolases Memory Rodentia Central nervous system dGTPase Environmental factor Esterases Protein Encephalon Learning Vertebrata Mammalia Acquisition process Mouse Animal Hydrolases Hypoxia Hippocampus
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Summary:	Abstract Spine-associated Rap-specific GTPase-activating protein (SPAR) is a postsynaptic protein that forms a complex with postsynaptic density (PSD)-95 and N -methyl- d -aspartate receptors (NMDARs), and morphologically regulates dendritic spines. Mild intermittent hypoxia (IH, 16.0% O2 , 4 h/day for 4 weeks) is known to markedly enhance spatial learning and memory in postnatal developing mice. Here, we report that this effect is correlated with persistent increases in SPAR expression as well as long-term potentiation (LTP) in the hippocampus of IH-exposed mice. Furthermore, an infusion of SPAR antisense oligonucleotides into the dorsal hippocampus disrupted elevation of SPAR expression, preventing enhanced hippocampal LTP in IH-exposed developing mice and also reducing LTP in normoxic mice, without altering basal synaptic transmission. In SPAR antisense-treated mice, acquisition of the Morris water maze spatial learning task was impaired, as was memory retention in probe trails following training. This study provides the first evidence that SPAR is functionally required for synaptic plasticity and contributes to the IH-induced enhancement of spatial learning and memory in postnatal developing mice.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2009.05.011