PMID- 10531425
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20240421
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 21
DP  - 1999 Nov 1
TI  - Knockdown of AMPA receptor GluR2 expression causes delayed neurodegeneration and 
      increases damage by sublethal ischemia in hippocampal CA1 and CA3 neurons.
PG  - 9218-27
AB  - Considerable evidence suggests that Ca(2+)-permeable AMPA receptors are critical 
      mediators of the delayed, selective neuronal death associated with transient 
      global ischemia and sustained seizures. Global ischemia suppresses mRNA and 
      protein expression of the glutamate receptor subunit GluR2 and increases AMPA 
      receptor-mediated Ca(2+) influx into vulnerable neurons of the hippocampal CA1 
      before the onset of neurodegeneration. Status epilepticus suppresses GluR2 mRNA 
      and protein in CA3 before neurodegeneration in this region. To examine whether 
      acute downregulation of the GluR2 subunit, even in the absence of a neurological 
      insult, can cause neuronal cell death, we performed GluR2 "knockdown" 
      experiments. Intracerebral injection of antisense oligodeoxynucleotides targeted 
      to GluR2 mRNA induced delayed death of pyramidal neurons in CA1 and CA3. 
      Antisense-induced neurodegeneration was preceded by a reduction in GluR2 mRNA, as 
      indicated by in situ hybridization, and in GluR2 protein, as indicated by Western 
      blot analysis. GluR2 antisense suppressed GluR2 mRNA in the dentate gyrus but did 
      not cause cell death. The AMPA receptor antagonist 
      6-cyano-7-nitroquinoxiline-2,3-dione (CNQX) and the Ca(2+)-permeable AMPA 
      receptor channel blocker 1-naphthyl acetyl spermine protected against 
      antisense-induced cell death. This result indicates that antisense-induced cell 
      death is mediated by Ca(2+)-permeable AMPA receptors. GluR2 antisense and brief 
      sublethal global ischemia acted synergistically to cause degeneration of 
      pyramidal neurons, consistent with action by a common mechanism. These findings 
      demonstrate that downregulation of GluR2 is sufficient to induce delayed death of 
      specific neuronal populations.
FAU - Oguro, K
AU  - Oguro K
AD  - Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 
      10461, USA.
FAU - Oguro, N
AU  - Oguro N
FAU - Kojima, T
AU  - Kojima T
FAU - Grooms, S Y
AU  - Grooms SY
FAU - Calderone, A
AU  - Calderone A
FAU - Zheng, X
AU  - Zheng X
FAU - Bennett, M V
AU  - Bennett MV
FAU - Zukin, R S
AU  - Zukin RS
LA  - eng
GR  - NS 007412/NS/NINDS NIH HHS/United States
GR  - T32 NS007412/NS/NINDS NIH HHS/United States
GR  - NS 20752/NS/NINDS NIH HHS/United States
GR  - R01 NS020752/NS/NINDS NIH HHS/United States
GR  - NS 31282/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Oligodeoxyribonucleotides, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, AMPA)
RN  - P6W5IXV8V9 (glutamate receptor ionotropic, AMPA 2)
SB  - IM
MH  - Animals
MH  - Brain/*pathology/physiopathology
MH  - Brain Ischemia/chemically induced/pathology/*physiopathology
MH  - Cell Survival/drug effects
MH  - Cerebral Ventricles/drug effects/physiology
MH  - Gene Expression Regulation/*drug effects
MH  - Hippocampus/pathology/physiopathology
MH  - Injections, Intraventricular
MH  - Male
MH  - Nerve Degeneration/chemically induced/pathology/*physiopathology
MH  - Neurons/pathology/physiology
MH  - Oligodeoxyribonucleotides, Antisense/*pharmacology
MH  - Protein Biosynthesis
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, AMPA/*genetics
MH  - Time Factors
MH  - Transcription, Genetic
PMC - PMC6782923
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
PMCR- 2000/05/01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
PHST- 2000/05/01 00:00 [pmc-release]
AID - 3561 [pii]
AID - 10.1523/JNEUROSCI.19-21-09218.1999 [doi]
PST - ppublish
SO  - J Neurosci. 1999 Nov 1;19(21):9218-27. doi: 10.1523/JNEUROSCI.19-21-09218.1999.