Differential role of the proteasome in the early and late phases of BDNF-induced facilitation of LTP.
J Neurosci
; 35(8): 3319-29, 2015 Feb 25.
Article
em En
| MEDLINE
| ID: mdl-25716833
ABSTRACT
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Potenciação de Longa Duração
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Fator Neurotrófico Derivado do Encéfalo
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Complexo de Endopeptidases do Proteassoma
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Região CA1 Hipocampal
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article