Impaired long-term potentiation in c-Jun N-terminal kinase 2-deficient mice

被引:44
作者
Chen, JT
Lu, DH
Chia, CP
Ruan, DY
Sabapathy, K [1 ]
Xiao, ZC
机构
[1] Singapore Gen Hosp, Dept Clin Res, Neurobiol Lab, Singapore 169608, Singapore
[2] Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China
[3] Natl Canc Ctr, Div Cell & Mol Biol, Mol Carcinogenesis Lab, Singapore, Singapore
[4] Cent S Univ, Xiangya Sch Med, Dept Anat & Neurobiol, Changsha, Hunan, Peoples R China
[5] Inst Mol & Cell Biol, Singapore, Singapore
关键词
c-Jun N-terminal kinase; long-term potentiation;
D O I
10.1111/j.1471-4159.2005.03037.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
c-Jun N-terminal kinases (JNKs) are thought to be involved in regulating synaptic plasticity. We therefore investigated the specific role of JNK2 in modulating long-term potentiation (LTP) in hippocampus during development, using JNK2-deficient mice. The morphological structure and the numbers of both NeuN, a specific neuronal marker, and GABA-positive neurons in the hippocampal areas were similar in wild-type and Jnk2(-/-) mice. Western blot analysis revealed that JNK2 expression was higher and stable at 1 and 3 months of age, but JNK1 levels were lower at 1 month of age and almost undetectable in 3-month-old wild-type mice. In contrast to wild-type mice, there was a significant increase in JNK1 expression in JNK2 mutant mice, especially at 1 month of age. Electrophysiological studies demonstrated that LTP was impaired in both the CA1 and CA3 regions in 1-month-old, but not in adult, Jnk2(-/-) mice, probably owing to decreased presynaptic neurotransmitter release. Moreover, late-phase LTP, but not early-phase LTP, was impaired in the Jnk2(-/-) adult mice, suggesting that JNK2 plays a role in transforming early LTP to late LTP. Together, the data highlight the specific role of JNK2 in hippocampal synaptic plasticity during development.
引用
收藏
页码:463 / 473
页数:11
相关论文
共 38 条
[1]   Toward a molecular definition of long-term memory storage [J].
Bailey, CH ;
Bartsch, D ;
Kandel, ER .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) :13445-13452
[2]   Role of β-catenin in synaptic vesicle localization and presynaptic assembly [J].
Bamji, SX ;
Shimazu, K ;
Kimes, N ;
Huelsken, J ;
Birchmeier, W ;
Lu, B ;
Reichardt, LF .
NEURON, 2003, 40 (04) :719-731
[3]   Inhibition of hippocampal Jun N-terminal kinase enhances short-term memory but blocks long-term memory formation and retrieval of an inhibitory avoidance task [J].
Bevilaqua, LRM ;
Kerr, DS ;
Medina, JH ;
Izquierdo, I ;
Cammarota, M .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2003, 17 (04) :897-902
[4]   Differential expression of SAPK isoforms in the rat brain. An in situ hybridisation study in the adult rat brain and during post-natal development [J].
Carboni, L ;
Carletti, R ;
Tacconi, S ;
Corti, C ;
Ferraguti, F .
MOLECULAR BRAIN RESEARCH, 1998, 60 (01) :57-68
[5]   JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins [J].
Chang, LF ;
Jones, Y ;
Ellisman, MH ;
Goldstein, LSB ;
Karin, M .
DEVELOPMENTAL CELL, 2003, 4 (04) :521-533
[6]   c-Jun N-terminal protein kinase (JNK) 2/3 is specifically activated by stress, mediating c-Jun activation, in the presence of constitutive JNK1 activity in cerebellar neurons [J].
Coffey, ET ;
Smiciene, G ;
Hongisto, V ;
Cao, J ;
Brecht, S ;
Herdegen, T ;
Courtney, MJ .
JOURNAL OF NEUROSCIENCE, 2002, 22 (11) :4335-4345
[7]   The role of c-Jun N-terminal kinase in the Aβ-mediated impairment of LTP and regulation of synaptic transmission in the hippocampus [J].
Costello, DA ;
Herron, CE .
NEUROPHARMACOLOGY, 2004, 46 (05) :655-662
[8]   A role for c-Jun N-terminal kinase in the inhibition of long-term potentiation by interleukin-1β and long-term depression in the rat dentate gyrus in vitro [J].
Curran, BP ;
Murray, HJ ;
O'Connor, JJ .
NEUROSCIENCE, 2003, 118 (02) :347-357
[9]   FOS - AN IMMEDIATE-EARLY TRANSCRIPTION FACTOR IN NEURONS [J].
CURRAN, T ;
MORGAN, JI .
JOURNAL OF NEUROBIOLOGY, 1995, 26 (03) :403-412
[10]   JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms [J].
David, JP ;
Sabapathy, K ;
Hoffmann, O ;
Idarraga, MH ;
Wagner, EF .
JOURNAL OF CELL SCIENCE, 2002, 115 (22) :4317-4325