PMID- 20505103
OWN - NLM
STAT- MEDLINE
DCOM- 20100615
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 30
IP  - 21
DP  - 2010 May 26
TI  - Activity-dependent augmentation of spontaneous neurotransmission during 
      endoplasmic reticulum stress.
PG  - 7358-68
LID - 10.1523/JNEUROSCI.5358-09.2010 [doi]
AB  - The endoplasmic reticulum (ER) is an essential cellular compartment responsible 
      for Ca(2+) sequestration, signaling, protein translation, folding as well as 
      transport. Several acute and chronic disease conditions impair ER function 
      leading to ER stress. To study the impact of ER stress on synaptic transmission 
      we applied tunicamycin (TM) or thapsigargin (TG) to hippocampal neurons, which 
      triggered sustained elevation of key ER stress markers. We monitored evoked and 
      spontaneous neurotransmission during 4 d of TM or TG treatment and detected only 
      a 20% increase in paired pulse depression suggesting an increase in 
      neurotransmitter release probability. However, the treatments did not 
      significantly affect the number of active synapses or the size of the total 
      recycling vesicle pool as measured by uptake and release of styryl dye FM1-43. In 
      contrast, under the same conditions, we observed a dramatic fourfold increase in 
      spontaneous excitatory transmission, which could be reversed by chronic treatment 
      with the NMDA receptor blocker AP-5 or by treatment with salubrinal, a selective 
      inhibitor of eukaryotic translation initiation factor 2 (eIF2alpha) 
      dephosphorylation. Furthermore, ER stress caused NMDA receptor-dependent 
      suppression of eukaryotic elongation factor-2 (eEF2) phosphorylation thus 
      reversing downstream signaling mediated by spontaneous release. Together, these 
      findings suggest that chronic ER stress augments spontaneous excitatory 
      neurotransmission and reverses its downstream signaling in a NMDA 
      receptor-dependent manner, which may contribute to neuronal circuitry 
      abnormalities that precede synapse degeneration in several neurological 
      disorders.
FAU - Nosyreva, Elena
AU  - Nosyreva E
AD  - Department of Neuroscience, University of Texas Southwestern Medical Center, 
      Dallas, Texas 75390-9111, USA.
FAU - Kavalali, Ege T
AU  - Kavalali ET
LA  - eng
GR  - R01 MH066198/MH/NIMH NIH HHS/United States
GR  - R01 MH068437/MH/NIMH NIH HHS/United States
GR  - R01 MH066198-08/MH/NIMH NIH HHS/United States
GR  - R01 MH066198-07/MH/NIMH NIH HHS/United States
GR  - R01 MH068437-05/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Ddit3 protein, mouse)
RN  - 0 (Elf2 protein, mouse)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (FM1 43)
RN  - 0 (GABA Antagonists)
RN  - 0 (Pyridinium Compounds)
RN  - 0 (Quaternary Ammonium Compounds)
RN  - 0 (Sodium Channel Blockers)
RN  - 0 (Transcription Factors)
RN  - 11089-65-9 (Tunicamycin)
RN  - 124-87-8 (Picrotoxin)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 4368-28-9 (Tetrodotoxin)
RN  - 67526-95-8 (Thapsigargin)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/pharmacology
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/metabolism
MH  - Endoplasmic Reticulum/*drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - GABA Antagonists/pharmacology
MH  - Hippocampus/cytology
MH  - Neurons/drug effects/*ultrastructure
MH  - Patch-Clamp Techniques/methods
MH  - Phosphorylation
MH  - Picrotoxin/pharmacology
MH  - Pyridinium Compounds/metabolism
MH  - Quaternary Ammonium Compounds/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sodium Channel Blockers/pharmacology
MH  - Synaptic Transmission/drug effects/*physiology
MH  - Tetrodotoxin/pharmacology
MH  - Thapsigargin/pharmacology
MH  - Transcription Factor CHOP/metabolism
MH  - Transcription Factors/metabolism
MH  - Tunicamycin/pharmacology
PMC - PMC2892630
MID - NIHMS208424
EDAT- 2010/05/28 06:00
MHDA- 2010/06/16 06:00
PMCR- 2010/11/26
CRDT- 2010/05/28 06:00
PHST- 2010/05/28 06:00 [entrez]
PHST- 2010/05/28 06:00 [pubmed]
PHST- 2010/06/16 06:00 [medline]
PHST- 2010/11/26 00:00 [pmc-release]
AID - 30/21/7358 [pii]
AID - 3600332 [pii]
AID - 10.1523/JNEUROSCI.5358-09.2010 [doi]
PST - ppublish
SO  - J Neurosci. 2010 May 26;30(21):7358-68. doi: 10.1523/JNEUROSCI.5358-09.2010.