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

• 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
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.05.011

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.