PMID- 12853306
OWN - NLM
STAT- MEDLINE
DCOM- 20030825
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 1749-6632 (Electronic)
IS  - 0077-8923 (Linking)
VI  - 993
DP  - 2003 May
TI  - 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.
PG  - 134-45; discussion 159-60
AB  - 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.
FAU - Jiang, Xueying
AU  - Jiang X
AD  - Department of Neurology and Neuroscience, Uniformed Services University of the 
      Health Sciences, Bethesda, Maryland 20814, USA.
FAU - Zhu, Daming
AU  - Zhu D
FAU - Okagaki, Peter
AU  - Okagaki P
FAU - Lipsky, Robert
AU  - Lipsky R
FAU - Wu, Xuan
AU  - Wu X
FAU - Banaudha, Krishna
AU  - Banaudha K
FAU - Mearow, Karen
AU  - Mearow K
FAU - Strauss, Kenneth I
AU  - Strauss KI
FAU - Marini, Ann M
AU  - Marini AM
LA  - eng
GR  - R01 NS038654/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Autocrine Communication
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism/pharmacology
MH  - Cells, Cultured
MH  - Cerebellum/cytology/drug effects/*metabolism
MH  - Genes, bcl-2
MH  - Glutamic Acid/toxicity
MH  - Ischemic Preconditioning/*methods
MH  - N-Methylaspartate/metabolism/pharmacology
MH  - NF-kappa B/metabolism
MH  - Neurons/cytology/drug effects/*metabolism
MH  - Neuroprotective Agents/*metabolism
MH  - Oligonucleotides, Antisense/metabolism
MH  - Receptor, trkB/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
PMC - PMC2597300
MID - NIHMS9281
EDAT- 2003/07/11 05:00
MHDA- 2003/08/26 05:00
PMCR- 2008/12/08
CRDT- 2003/07/11 05:00
PHST- 2003/07/11 05:00 [pubmed]
PHST- 2003/08/26 05:00 [medline]
PHST- 2003/07/11 05:00 [entrez]
PHST- 2008/12/08 00:00 [pmc-release]
AID - 10.1111/j.1749-6632.2003.tb07522.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2003 May;993:134-45; discussion 159-60. doi: 
      10.1111/j.1749-6632.2003.tb07522.x.