N-methyl-D-aspartate and TrkB receptor activation in cerebellar granule cells -: An in vitro model of preconditioning to stimulate intrinsic survival pathways in neurons

被引:62
作者
Jiang, XY
Zhu, DM
Okagaki, P
Lipsky, R
Wu, X
Banaudha, K
Mearow, K
Strauss, KI
Marini, AM
机构
[1] Uniformed Serv Univ Hlth Sci, Dept Neurol & Neurosci, Bethesda, MD 20814 USA
[2] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA
[3] Mem Univ Newfoundland, Fac Med, St Johns, NF, Canada
来源
NEUROPROTECTIVE AGENTS | 2003年 / 993卷
关键词
N-methyl-D-aspartate; TrkB; receptor activation; cerebellar granular cells; survival pathways; neurons;
D O I
10.1111/j.1749-6632.2003.tb07522.x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Delineating the mechanisms of survival pathways that exist in neurons will provide important insight into how neurons utilize intracellular proteins as neuroprotectants against the causes of acute neurodegeneration. We have employed cultured rat cerebellar granule cells as a model for determining the mechanisms of these intraneuronal survival pathways. Glutamate has long been known to kill neurons by an N-methyl-D-aspartate (NMDA) receptor-mediated mechanism. Paradoxically, subtoxic concentrations of NMDA protect neurons against glutamate-mediated excitotoxicity. Because NMDA protects neurons in physiologic concentrations of glucose and oxygen, we refer to this phenomenon as physiologic preconditioning. One of the major mechanisms of NMDA neuroprotection involves the activation of NMDA receptors leading to the rapid release of brain-derived neurotrophic factor (BDNF). BDNF then binds to and activates its cognate receptor, receptor tyrosine kinase B (TrkB). The efficient utilization of these two, receptors confers remarkable resistance against millimolar concentrations of glutamate that kill more than eighty percent of the neurons in the absence of preconditioning the neurons with a subtoxic concentration of NMDA. Exactly how the neurons mediate neuroprotection by activation of both receptors is just beginning to be understood. Both NMDA and TrkB receptors activate nuclear factor kappaB (NF-kappaB), a transcription factor known to be involved in protecting neurons against many different kinds of toxic insults. By converging on survival transcription factors, such as NF-kappaB, NMDA and TrkB receptors protect neurons. Thus, crosstalk between these very different receptors provides a rapid means of neuronal communication to upregulate survival proteins through release and transcriptional activation of messenger RNA.
引用
收藏
页码:134 / 145
页数:12
相关论文
共 48 条
  • [1] Abe H, 1996, ACTA NEUROBIOL EXP, V56, P3, DOI 10.55782/ane-1996-1096
  • [2] A BDNF AUTOCRINE LOOP IN ADULT SENSORY NEURONS PREVENTS CELL DEATH
    ACHESON, A
    CONOVER, JC
    FANDL, JP
    DECHIARA, TM
    RUSSELL, M
    THADANI, A
    SQUINTO, SP
    YANCOPOULOS, GD
    LINDSAY, RM
    [J]. NATURE, 1995, 374 (6521) : 450 - 453
  • [3] BAEUERLE PA, 1994, ANNU REV IMMUNOL, V12, P141, DOI 10.1146/annurev.immunol.12.1.141
  • [4] AMPA prevents glutamate-induced neurotoxicity and apoptosis in cultured cerebellar granule cell neurons
    Banaudha, Krishna
    Marini, Ann M.
    [J]. NEUROTOXICITY RESEARCH, 2000, 2 (01) : 51 - 61
  • [5] Ischemic preconditioning and brain tolerance - Temporal histological and functional outcomes, protein synthesis requirement, and interleukin-1 receptor antagonist and early gene expression
    Barone, FC
    White, RF
    Spera, PA
    Ellison, J
    Currie, RW
    Wang, XK
    Feuerstein, GZ
    [J]. STROKE, 1998, 29 (09) : 1937 - 1950
  • [6] THE I-KAPPA-B PROTEINS - MULTIFUNCTIONAL REGULATORS OF REL/NF-KAPPA-B TRANSCRIPTION FACTORS
    BEG, AA
    BALDWIN, AS
    [J]. GENES & DEVELOPMENT, 1993, 7 (11) : 2064 - 2070
  • [7] CENTRAL OF I-KAPPA-B-ALPHA PROTEOLYSIS BY SITE-SPECIFIC, SIGNAL-INDUCED PHOSPHORYLATION
    BROWN, K
    GERSTBERGER, S
    CARLSON, L
    FRANZOSO, G
    SIEBENLIST, U
    [J]. SCIENCE, 1995, 267 (5203) : 1485 - 1488
  • [8] Asymmetric propagation of spreading depression along the anteroposterior axis of the cerebral cortex in mice
    Godukhin, OV
    Obrenovitch, TP
    [J]. JOURNAL OF NEUROPHYSIOLOGY, 2001, 86 (04) : 2109 - 2111
  • [9] Grabb MC, 1999, J NEUROSCI, V19, P1657
  • [10] SYNAPTIC ACTIVATION OF NF-KAPPA-B BY GLUTAMATE IN CEREBELLAR GRANULE NEURONS IN-VITRO
    GUERRINI, L
    BLASI, F
    DENISDONINI, S
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (20) : 9077 - 9081