Hippocampal CREB1 but not CREB2 is decreased in aged rats with spatial memory impairments

被引:67
作者
Brightwell, JJ [1 ]
Gallagher, M
Colombo, PJ
机构
[1] Tulane Univ, Neurosci Program, New Orleans, LA 70118 USA
[2] Tulane Univ, Dept Psychol, New Orleans, LA 70118 USA
[3] Johns Hopkins Univ, Dept Psychol, Baltimore, MD 21218 USA
关键词
transcription factor; Morris water maze; memory; CREB; aging;
D O I
10.1016/j.nlm.2003.08.001
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Recent evidence has shown that abnormal signal transduction is related to non-pathological memory impairment among aged subjects. Members of the CREB family of transcription factors contain enhancers (i.e., CREB1) and repressors (i.e., CREB2) of transcription and interact with numerous signaling proteins to mediate the transition from short-term to long-term memory. In this study, quantitative Western blotting was used to determine the levels of CREB1 and CREB2 in homogenates from hippocampi of individual 6- and 24-month-old male Long-Evans rats trained first on a place-learning task in the Morris water maze, then on a transfer task. Based on spatial memory performance, aged rats were characterized into two groups; aged-unimpaired rats (AU) had scores within the range of the young (Y) and aged-impaired rats (AI) fell outside of that range. Overall, CREB1 protein was significantly lower in aged rats in comparison with young rats. Aposteriori analysis showed that this difference was due to a significant decrease in CREB1 levels among aged-impaired rats, whereas aged-unimpaired rats had CREB1 levels comparable to young rats. There was no significant change in levels of CREB2 protein between young and aged rats. These results show that the dysregulation of CREB1 protein may contribute to the spatial memory deficits observed among some aged subjects. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:19 / 26
页数:8
相关论文
共 50 条
[1]   Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor [J].
Asanuma, M ;
Nishibayashi, S ;
Iwata, E ;
Kondo, Y ;
Nakanishi, T ;
Vargas, MG ;
Ogawa, N .
MOLECULAR BRAIN RESEARCH, 1996, 41 (1-2) :210-215
[2]   Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway [J].
Bach, ME ;
Barad, M ;
Son, H ;
Zhuo, M ;
Lu, YF ;
Shih, R ;
Mansuy, I ;
Hawkins, RD ;
Kandel, ER .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (09) :5280-5285
[3]   MEMORY DEFICITS ASSOCIATED WITH SENESCENCE - NEUROPHYSIOLOGICAL AND BEHAVIORAL-STUDY IN THE RAT [J].
BARNES, CA .
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY, 1979, 93 (01) :74-104
[4]   AGING AND THE PHYSIOLOGY OF SPATIAL MEMORY [J].
BARNES, CA .
NEUROBIOLOGY OF AGING, 1988, 9 (5-6) :563-568
[5]   APLYSIA CREB2 REPRESSES LONG-TERM FACILITATION - RELIEF OF REPRESSION CONVERTS TRANSIENT FACILITATION INTO LONG-TERM FUNCTIONAL AND STRUCTURAL-CHANGE [J].
BARTSCH, D ;
GHIRARDI, M ;
SKEHEL, PA ;
KARL, KA ;
HERDER, SP ;
CHEN, M ;
BAILEY, CH ;
KANDEL, ER .
CELL, 1995, 83 (06) :979-992
[6]   Targeting of the CREB gene leads to up-regulation of a novel CREB mRNA isoform [J].
Blendy, JA ;
Kaestner, KH ;
Schmid, W ;
Gass, P ;
Schutz, G .
EMBO JOURNAL, 1996, 15 (05) :1098-1106
[7]   A SYNAPTIC MODEL OF MEMORY - LONG-TERM POTENTIATION IN THE HIPPOCAMPUS [J].
BLISS, TVP ;
COLLINGRIDGE, GL .
NATURE, 1993, 361 (6407) :31-39
[8]   DEFICIENT LONG-TERM-MEMORY IN MICE WITH A TARGETED MUTATION OF THE CAMP-RESPONSIVE ELEMENT-BINDING PROTEIN [J].
BOURTCHULADZE, R ;
FRENGUELLI, B ;
BLENDY, J ;
CIOFFI, D ;
SCHUTZ, G ;
SILVA, AJ .
CELL, 1994, 79 (01) :59-68
[9]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[10]   Molecular enhancement of memory formation [J].
Carew, TJ .
NEURON, 1996, 16 (01) :5-8