PMID- 18441292
OWN - NLM
STAT- MEDLINE
DCOM- 20080721
LR  - 20240317
IS  - 1549-5485 (Electronic)
IS  - 1072-0502 (Print)
IS  - 1072-0502 (Linking)
VI  - 15
IP  - 5
DP  - 2008 May
TI  - Proteasome inhibition enhances the induction and impairs the maintenance of 
      late-phase long-term potentiation.
PG  - 335-47
LID - 10.1101/lm.984508 [doi]
AB  - Protein degradation by the ubiquitin-proteasome pathway plays important roles in 
      synaptic plasticity, but the molecular mechanisms by which proteolysis regulates 
      synaptic strength are not well understood. We investigated the role of the 
      proteasome in hippocampal late-phase long-term potentiation (L-LTP), a model for 
      enduring synaptic plasticity. We show here that inhibition of the proteasome 
      enhances the induction of L-LTP, but inhibits its maintenance. Proteasome 
      inhibitor-mediated enhancement of the early part of L-LTP requires activation of 
      NMDA receptors and the cAMP-dependent protein kinase. Augmentation of L-LTP 
      induction by proteasome inhibition is blocked by a protein synthesis inhibitor 
      anisomycin and is sensitive to the drug rapamycin. Our findings indicate that 
      proteasome inhibition increases the induction of L-LTP by stabilizing locally 
      translated proteins in dendrites. In addition, our data show that inhibition of 
      the proteasome blocks transcription of brain-derived neurotrophic factor (BDNF), 
      which is a cAMP-responsive element-binding protein (CREB)-inducible gene. 
      Furthermore, our results demonstrate that the proteasome inhibitors block 
      degradation of ATF4, a CREB repressor. Thus, proteasome inhibition appears to 
      hinder CREB-mediated transcription. Our results indicate that blockade of 
      proteasome activity obstructs the maintenance of L-LTP by interfering with 
      transcription as well as translation required to sustain L-LTP. Thus, 
      proteasome-mediated proteolysis has different roles during the induction and the 
      maintenance of L-LTP.
FAU - Dong, Chenghai
AU  - Dong C
AD  - Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, 
      Winston-Salem, North Carolina 27157, USA.
FAU - Upadhya, Sudarshan C
AU  - Upadhya SC
FAU - Ding, Lan
AU  - Ding L
FAU - Smith, Thuy K
AU  - Smith TK
FAU - Hegde, Ashok N
AU  - Hegde AN
LA  - eng
GR  - R01 MH060225/MH/NIMH NIH HHS/United States
GR  - MH060225/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080425
PL  - United States
TA  - Learn Mem
JT  - Learning & memory (Cold Spring Harbor, N.Y.)
JID - 9435678
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Ubiquitin)
RN  - 6C74YM2NGI (Anisomycin)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Animals
MH  - Anisomycin/administration & dosage/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Cyclic AMP Response Element-Binding Protein/genetics
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Dendrites/metabolism
MH  - Hippocampus/drug effects
MH  - Long-Term Potentiation/*drug effects
MH  - Mice
MH  - Neuronal Plasticity/drug effects
MH  - Peptide Hydrolases/pharmacology
MH  - *Proteasome Inhibitors
MH  - Protein Biosynthesis/drug effects/genetics
MH  - Protein Synthesis Inhibitors/administration & dosage/*pharmacology
MH  - RNA, Messenger/drug effects
MH  - Receptors, N-Methyl-D-Aspartate/drug effects
MH  - Synapses/drug effects
MH  - Transcriptional Activation/drug effects/genetics
MH  - Ubiquitin/*drug effects
PMC - PMC2364605
EDAT- 2008/04/29 09:00
MHDA- 2008/07/22 09:00
PMCR- 2009/05/01
CRDT- 2008/04/29 09:00
PHST- 2008/04/29 09:00 [pubmed]
PHST- 2008/07/22 09:00 [medline]
PHST- 2008/04/29 09:00 [entrez]
PHST- 2009/05/01 00:00 [pmc-release]
AID - 15/5/335 [pii]
AID - 10.1101/lm.984508 [doi]
PST - epublish
SO  - Learn Mem. 2008 Apr 25;15(5):335-47. doi: 10.1101/lm.984508. Print 2008 May.