Differential effects of hypoxia-ischemia on subunit expression and tyrosine phosphorylation of the NMDA receptor in 7-and 21-day-old rats

被引:33
作者
Gurd, JW [1 ]
Bissoon, N
Beesley, PW
Nakazawa, T
Yamamoto, T
Vannucci, SJ
机构
[1] Univ Toronto, Div Life Sci, Ctr Neurobiol Stress, Toronto, ON M1C 1A4, Canada
[2] Univ London Royal Holloway & Bedford New Coll, Sch Biol Sci, Egham TW20 0EX, Surrey, England
[3] Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo, Japan
[4] Penn State Univ, Milton S Hershey Med Ctr, Dept Pediat, Div Neurol, Hershey, PA 17033 USA
关键词
hypoxia-ischemia; ischemia; NMDA receptor; tyrosine phosphorylation;
D O I
10.1046/j.1471-4159.2002.01026.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
The effect of cerebral hypoxia-ischemia (HI) on levels and tyrosine phosphorylation of the NMDA receptor was examined in 7- (P7) and 21 (P21)-day-old rats. Unilateral HI was administered by ligation of the right common carotid artery and exposure to an atmosphere of 8% O-2 /92% N-2 for 2 (P7) or 1.5 (P21) h. This duration of HI produces significant infarction in nearly all of the survivors with damage being largely restricted to the cortex, striatum, and hippocampus of the hemisphere ipsilateral to the carotid artery ligation. NR2A levels in the right hemisphere of P7 pups were markedly reduced after 24 h of recovery, while NR1 and NR2B remained unchanged. In contrast, NR2B, but not NR2A, was reduced after HI at P21. At both ages, HI resulted in a transient increase in tyrosine phosphorylation of a number of forebrain proteins that peaked between 1 and 6 h of recovery. At both P7 and P21, tyrosine phosphorylation of NR2B was enhanced 1 h after HI and had returned to basal levels by 24 h. HI induced an increase in tyrosine phosphorylation of NR2A in 21 day, but not in 7-day-old animals. The differential effects of HI on the NMDA receptor at different post-natal ages may contribute to changing sensitivity to hypoxia-ischemia.
引用
收藏
页码:848 / 856
页数:9
相关论文
共 64 条
[31]   PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL ROLES OF EXCITATORY AMINO-ACIDS DURING CENTRAL-NERVOUS-SYSTEM DEVELOPMENT [J].
MCDONALD, JW ;
JOHNSTON, MV .
BRAIN RESEARCH REVIEWS, 1990, 15 (01) :41-70
[32]   DEVELOPMENTAL AND REGIONAL EXPRESSION IN THE RAT-BRAIN AND FUNCTIONAL-PROPERTIES OF 4 NMDA RECEPTORS [J].
MONYER, H ;
BURNASHEV, N ;
LAURIE, DJ ;
SAKMANN, B ;
SEEBURG, PH .
NEURON, 1994, 12 (03) :529-540
[33]   HETEROMERIC NMDA RECEPTORS - MOLECULAR AND FUNCTIONAL DISTINCTION OF SUBTYPES [J].
MONYER, H ;
SPRENGEL, R ;
SCHOEPFER, R ;
HERB, A ;
HIGUCHI, M ;
LOMELI, H ;
BURNASHEV, N ;
SAKMANN, B ;
SEEBURG, PH .
SCIENCE, 1992, 256 (5060) :1217-1221
[34]   MOLECULAR-CLONING AND CHARACTERIZATION OF THE RAT NMDA RECEPTOR [J].
MORIYOSHI, K ;
MASU, M ;
ISHII, T ;
SHIGEMOTO, R ;
MIZUNO, N ;
NAKANISHI, S .
NATURE, 1991, 354 (6348) :31-37
[35]   MOLECULAR DIVERSITY OF GLUTAMATE RECEPTORS AND IMPLICATIONS FOR BRAIN-FUNCTION [J].
NAKANISHI, S .
SCIENCE, 1992, 258 (5082) :597-603
[36]   Characterization of Fyn-mediated tyrosine phosphorylation sites on GluRε2 (NR2B) subunit of the N-methyl-D-aspartate receptor [J].
Nakazawa, T ;
Komai, S ;
Tezuka, T ;
Hisatsune, C ;
Umemori, H ;
Semba, K ;
Mishina, M ;
Manabe, T ;
Yamamoto, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (01) :693-699
[37]   Motoneuron-specific expression of NR3B, a novel NMDA-type glutamate receptor subunit that works in a dominant-negative manner [J].
Nishi, M ;
Hinds, H ;
Lu, HP ;
Kawata, M ;
Hayashi, Y .
JOURNAL OF NEUROSCIENCE, 2001, 21 (23) :art. no.-RC185
[38]   Delayed neuronal death in ischemic hippocampus involves stimulation of protein tyrosine phosphorylation [J].
Ohtsuki, T ;
Matsumoto, M ;
Kitagawa, K ;
Mabuchi, T ;
Mandai, K ;
Matsushita, K ;
Kuwabara, K ;
Tagaya, M ;
Ogawa, S ;
Ueda, H ;
Kamada, T ;
Yanagihara, T .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1996, 271 (04) :C1085-C1097
[39]   UP-REGULATION OF CALPAIN ACTIVITY IN NEONATAL RAT-BRAIN AFTER HYPOXIC-ISCHEMIA [J].
OSTWALD, K ;
HAGBERG, H ;
ANDINE, P ;
KARLSSON, JO .
BRAIN RESEARCH, 1993, 630 (1-2) :289-294
[40]   NMDA blockade attenuates caspase-3 activation and DNA fragmentation after neonatal hypoxia-ischemia [J].
Puka-Sundvall, M ;
Hallin, U ;
Zhu, CL ;
Wang, XY ;
Karlsson, JO ;
Blomgren, K ;
Hagberg, H .
NEUROREPORT, 2000, 11 (13) :2833-2836