PMID- 25716833
OWN - NLM
STAT- MEDLINE
DCOM- 20150629
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 35
IP  - 8
DP  - 2015 Feb 25
TI  - Differential role of the proteasome in the early and late phases of BDNF-induced 
      facilitation of LTP.
PG  - 3319-29
LID - 10.1523/JNEUROSCI.4521-14.2015 [doi]
AB  - The neurotrophin brain-derived neurotrophic factor (BDNF) mediates 
      activity-dependent long-term changes of synaptic strength in the CNS. The effects 
      of BDNF are partly mediated by stimulation of local translation, with consequent 
      alterations in the synaptic proteome. The ubiquitin-proteasome system (UPS) also 
      plays an important role in protein homeostasis at the synapse by regulating 
      synaptic activity. However, whether BDNF acts on the UPS to mediate the effects 
      on long-term synaptic potentiation (LTP) has not been investigated. In the 
      present study, we show similar and nonadditive effects of BDNF and proteasome 
      inhibition on the early phase of synaptic potentiation (E-LTP) induced by 
      theta-burst stimulation of rat hippocampal CA1 synapses. The effects of BDNF were 
      blocked by the proteasome activator IU1, suggesting that the neurotrophin acts by 
      decreasing proteasome activity. Accordingly, BDNF downregulated the proteasome 
      activity in cultured hippocampal neurons and in hippocampal synaptoneurosomes. 
      Furthermore, BDNF increased the activity of the deubiquitinating enzyme UchL1 in 
      synaptoneurosomes and upregulated free ubiquitin. In contrast to the effects on 
      posttetanic potentiation, proteasome activity was required for BDNF-mediated LTP. 
      These results show a novel role for BDNF in UPS regulation at the synapse, which 
      is likely to act together with the increased translation activity in the 
      regulation of the synaptic proteome during E-LTP.
CI  - Copyright (c) 2015 the authors 0270-6474/15/353319-11$15.00/0.
FAU - Santos, Ana Rita
AU  - Santos AR
AUID- ORCID: 0000-0003-1603-6721
AD  - Center for Neuroscience and Cell Biology.
FAU - Mele, Miranda
AU  - Mele M
AD  - Center for Neuroscience and Cell Biology, Institute for Interdisciplinary 
      Research, and.
FAU - Vaz, Sandra H
AU  - Vaz SH
AD  - Institute of Pharmacology and Neurosciences, Faculty of Medicine, and Unit of 
      Neurosciences, Institute of Molecular Medicine, University of Lisbon, 1649-028 
      Lisbon, Portugal.
FAU - Kellermayer, Blanka
AU  - Kellermayer B
AD  - Center for Neuroscience and Cell Biology.
FAU - Grimaldi, Maddalena
AU  - Grimaldi M
AUID- ORCID: 0000-0002-9254-1183
AD  - Center for Neuroscience and Cell Biology.
FAU - Colino-Oliveira, Mariana
AU  - Colino-Oliveira M
AD  - Institute of Pharmacology and Neurosciences, Faculty of Medicine, and Unit of 
      Neurosciences, Institute of Molecular Medicine, University of Lisbon, 1649-028 
      Lisbon, Portugal.
FAU - Rombo, Diogo M
AU  - Rombo DM
AUID- ORCID: 0000-0002-9922-7381
AD  - Institute of Pharmacology and Neurosciences, Faculty of Medicine, and Unit of 
      Neurosciences, Institute of Molecular Medicine, University of Lisbon, 1649-028 
      Lisbon, Portugal.
FAU - Comprido, Diogo
AU  - Comprido D
AD  - Center for Neuroscience and Cell Biology.
FAU - Sebastiao, Ana M
AU  - Sebastiao AM
AD  - Institute of Pharmacology and Neurosciences, Faculty of Medicine, and Unit of 
      Neurosciences, Institute of Molecular Medicine, University of Lisbon, 1649-028 
      Lisbon, Portugal.
FAU - Duarte, Carlos B
AU  - Duarte CB
AD  - Center for Neuroscience and Cell Biology, Department of Life Sciences, University 
      of Coimbra, 3004-504 Coimbra, Portugal, and cbduarte@ci.uc.pt.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (1-(1-(4-fluorophenyl)-2,5-dimethylpyrrol-3-yl)-2-pyrrolidin-1-ylethanone)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Pyrroles)
RN  - 0 (Pyrrolidines)
RN  - 0 (Ubiquitin)
RN  - EC 3.4.19.12 (UCHL1 protein, rat)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - CA1 Region, Hippocampal/*metabolism/physiology
MH  - Cells, Cultured
MH  - *Long-Term Potentiation
MH  - Male
MH  - Proteasome Endopeptidase Complex/drug effects/*metabolism
MH  - Pyrroles/pharmacology
MH  - Pyrrolidines/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Synaptosomes/drug effects/metabolism
MH  - Theta Rhythm
MH  - Ubiquitin/metabolism
MH  - Ubiquitin Thiolesterase/metabolism
PMC - PMC6605551
OTO - NOTNLM
OT  - BDNF
OT  - LTP
OT  - deubiquitinating enzymes
OT  - proteasome
OT  - synaptic plasticity
EDAT- 2015/02/27 06:00
MHDA- 2015/06/30 06:00
PMCR- 2015/08/25
CRDT- 2015/02/27 06:00
PHST- 2015/02/27 06:00 [entrez]
PHST- 2015/02/27 06:00 [pubmed]
PHST- 2015/06/30 06:00 [medline]
PHST- 2015/08/25 00:00 [pmc-release]
AID - 35/8/3319 [pii]
AID - 4521-14 [pii]
AID - 10.1523/JNEUROSCI.4521-14.2015 [doi]
PST - ppublish
SO  - J Neurosci. 2015 Feb 25;35(8):3319-29. doi: 10.1523/JNEUROSCI.4521-14.2015.