PMID- 17492691
OWN - NLM
STAT- MEDLINE
DCOM- 20070907
LR  - 20191210
IS  - 1050-9631 (Print)
IS  - 1050-9631 (Linking)
VI  - 17
IP  - 7
DP  - 2007
TI  - Subtoxic N-methyl-D-aspartate delayed neuronal death in ischemic brain injury 
      through TrkB receptor- and calmodulin-mediated PI-3K/Akt pathway activation.
PG  - 525-37
AB  - Previous studies have shown that subtoxic NMDA moderated the neuronal survival in 
      vitro and vivo. We performed this experiment to clarify the precise mechanism 
      underlie subtoxic NMDA delayed neuronal death in ischemic brain injury. We found 
      that pretreatment of NMDA (100 mg/kg) increased the number of the surviving CA1 
      pyramidal cells of hippocampus at 5 days of reperfusion. This dose of NMDA could 
      also enhance Akt activation after ischemia/reperfusion (I/R). Here, we examined 
      the possible mechanism that NMDA induced Akt activation. On the one hand, we 
      found NMDA receptor-mediated Akt activation was associated with increased 
      expression of BDNF (brain-derived neurotrophic factor) and activation of its 
      high-affinity receptor TrkB after I/R in the hippocampus CA1 region, which could 
      be held down by TrkB receptor antagonist K252a. On the other hand, we found that 
      NMDA enhanced the binding of Ca2+-dependent calmodulin (CaM) to p85 (the 
      regulation subunit of PI-3K), which led to the activation of Akt. W-13, an active 
      CaM inhibitor, prevented the combination of CaM and p85 and subsequent Akt 
      activation. Furthermore, NMDA receptor-mediated Akt activation was reversed by 
      combined treatment with LY294002, the specific blockade of PI-3K. Taken together, 
      our results suggested that subtoxic NMDA exerts the neuroprotective effect via 
      activation of prosurvival PI-3K/Akt pathway against ischemic brain injury, and 
      BDNF-TrkB signaling and Ca2+-dependent CaM cascade might contribute to NMDA 
      induced activation of PI-3K/Akt pathway.
CI  - (c) 2007 Wiley-Liss, Inc.
FAU - Xu, Jing
AU  - Xu J
AD  - Research Center for Biochemistry and Molecular Biology, The Jiangsu Key 
      Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Jiangsu, 
      People's Republic of China.
FAU - Zhang, Quan-Guang
AU  - Zhang QG
FAU - Li, Chong
AU  - Li C
FAU - Zhang, Guang-Yi
AU  - Zhang GY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calmodulin)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Subunits)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Brain Infarction/chemically induced/metabolism/physiopathology
MH  - Brain Ischemia/*metabolism/physiopathology
MH  - Brain-Derived Neurotrophic Factor/drug effects/metabolism
MH  - Calcium Signaling/drug effects/physiology
MH  - Calmodulin/*metabolism
MH  - Cell Survival/drug effects/physiology
MH  - Enzyme Activation/drug effects/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Hippocampus/drug effects/metabolism/physiopathology
MH  - Male
MH  - N-Methylaspartate/metabolism/*pharmacology
MH  - Nerve Degeneration/*drug therapy/physiopathology/prevention & control
MH  - Neuroprotective Agents/metabolism/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Subunits/drug effects/metabolism
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism
MH  - Pyramidal Cells/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/agonists/antagonists & inhibitors/*metabolism
MH  - Reperfusion Injury/metabolism/physiopathology
MH  - Signal Transduction/drug effects/physiology
EDAT- 2007/05/12 09:00
MHDA- 2007/09/08 09:00
CRDT- 2007/05/12 09:00
PHST- 2007/05/12 09:00 [pubmed]
PHST- 2007/09/08 09:00 [medline]
PHST- 2007/05/12 09:00 [entrez]
AID - 10.1002/hipo.20289 [doi]
PST - ppublish
SO  - Hippocampus. 2007;17(7):525-37. doi: 10.1002/hipo.20289.