Increased levels of D-aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility

被引:78
作者
Errico, Francesco [1 ]
Nistico, Robert [2 ,3 ]
Palma, Giuseppe [1 ]
Federici, Mauro [2 ]
Affuso, Andrea [4 ]
Brilli, Elisa [5 ]
Topo, Enza [6 ]
Centonze, Diego [2 ,7 ]
Bernardi, Giorgio [2 ,7 ]
Bozzi, Yuri [5 ]
D'Aniello, Antimo [6 ]
Di Lauro, Roberto [4 ]
Mercuri, Nicola B. [2 ,7 ]
Usiello, Alessandro [1 ,8 ]
机构
[1] CEINGE Biotecnol Avanzate, Lab Behav Neurosci, I-80145 Naples, Italy
[2] CERC Fdn Santa Lucia, Rome, Italy
[3] Univ Calabria, Dept Pharmacobiol, I-87036 Cosenza, Italy
[4] Biogem SCArL, IRGS, Avellino, Italy
[5] CNR, Ist Neurosci, I-56100 Pisa, Italy
[6] Staz Zool A Dohrn, Dept Neurobiol, Naples, Italy
[7] Univ Tor Vergata, Neurol Clin, Rome, Italy
[8] Univ Molise, Dept Hlth Sci, Campobasso, Italy
关键词
D-aspartate; hippocamus; NMDA receptors; long-term potentiation; Morris water maze; cognitive flexibility;
D O I
10.1016/j.mcn.2007.09.012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the present study, we demonstrate a direct role for D-aspartate in regulating hippocampal synaptic plasticity. These evidences were obtained using two different experimental strategies which enabled a non-physiological increase of endogenous D-aspartate levels in the mouse hippocampus: a genetic approach based on the targeted deletion Of D-aspartate oxidase gene and another based on the oral administration of D-aspartate. Overall, our results indicate that increased D-aspartate content does not affect basal properties of synaptic transmission but enhances long-term potentiation in hippocampal slices from both genetic and pharmacological animal models. Besides electrophysiological data, behavioral analysis suggests that altered levels Of D-aspartate in the hippocampus do not perturb basal spatial learning and memory abilities, but may selectively interfere with the dynamic NMDAR-dependent processes underlying cognitive flexibility. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:236 / 246
页数:11
相关论文
共 49 条
[41]   Characterization of electrically evoked [3H]-D-aspartate release from hippocampal slices [J].
Savage, DD ;
Galindo, R ;
Queen, SA ;
Paxton, LL ;
Allan, AM .
NEUROCHEMISTRY INTERNATIONAL, 2001, 38 (03) :255-267
[42]   D-aspartate localizations imply neuronal and neuroendocrine roles [J].
Schell, MJ ;
Cooper, OB ;
Snyder, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (05) :2013-2018
[43]   The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory [J].
Tsien, JZ ;
Huerta, PT ;
Tonegawa, S .
CELL, 1996, 87 (07) :1327-1338
[44]   D-ASPARTATE OXIDASE, A PEROXISOMAL ENZYME IN LIVER OF RAT AND MAN [J].
VANVELDHOVEN, PP ;
BREES, C ;
MANNAERTS, GP .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1073 (01) :203-208
[45]   Comparison of effects of DL-threo-β-benzyloxyaspartate (DL-TBOA) and L-trans-pyrrolidine-2,4-dicarboxylate (t-2,4-PDC) on uptake and release of [3H]D-aspartate in astrocytes and glutamatergic neurons [J].
Waagepetersen, HS ;
Shimamoto, K ;
Schousboe, A .
NEUROCHEMICAL RESEARCH, 2001, 26 (06) :661-666
[46]   EXCITATORY AMINO-ACID TRANSMITTERS [J].
WATKINS, JC ;
EVANS, RH .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1981, 21 :165-204
[47]   D-aspartate disposition in neuronal and endocrine tissues: Ontogeny, biosynthesis and release [J].
Wolosker, H ;
D'Aniello, A ;
Snyder, SH .
NEUROSCIENCE, 2000, 100 (01) :183-189
[48]   Cellular and subcellular distribution of D-aspartate oxidase in human and rat brain [J].
Zaar, K ;
Köst, HP ;
Schad, A ;
Völkl, A ;
Baumgart, E ;
Fahimi, HD .
JOURNAL OF COMPARATIVE NEUROLOGY, 2002, 450 (03) :272-282
[49]   ALTERNATIVELY SPLICED ISOFORMS OF THE NMDARI RECEPTOR SUBUNIT [J].
ZUKIN, RS ;
BENNETT, MVL .
TRENDS IN NEUROSCIENCES, 1995, 18 (07) :306-313