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Phosphorylation Changes of CaMKII, ERK1/2, PKB/Akt Kinases and CREB Activation During Early Long-Term Potentiation at Schaffer Collateral-CA1 Mouse Hippocampal Synapses

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Abstract

Protein phosphorylation is the main signaling system known to trigger synaptic changes underlying long-term potentiation (LTP). The timing of these phosphorylations plays an essential role to maintain the potentiated state of synapses. However, in mice a simultaneous analysis of phosphorylated proteins during early-LTP (E-LTP) has not been thoroughly carried out. Here we described phosphorylation changes of αCaMKII, ERK1/2, PKB/Akt and CREB at different times after E-LTP induced at Schaffer collateral/commissural fiber-CA1 synapses by 1 s 100 Hz tetanic stimulation in mouse hippocampal slices. We found that phosphorylation levels of all the molecules examined rapidly increased after tetanisation and remained above the basal level up to 30 min. Notably, we observed a sustained increment in the phosphorylation level of Akt at Ser473, whereas the phosphorylation level of Akt at Thr308 was unchanged. Unexpectedly, we also detected a marked increase of CREB target genes expression levels, c-fos, Egr-1 and exon-III containing BDNF transcripts. Our findings, besides providing a detailed timing of phosphorylation of the major kinases involved in E-LTP in mice, revealed that a modest LTP induction paradigm specifically triggers CREB-mediated gene expression.

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Acknowledgments

This study was supported in part by the Italian Ministry of Health—Research Project Neurodegenerative Diseases, ex art. 56: “Role of Herpes Simplex-I infection in the pathogenesis of Alzheimer’s Disease and transmissible spongiform encephalopathies”.

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Authors and Affiliations

  1. IRCCS San Raffaele Pisana, Via dei Bonacolsi 81, 00163, Rome, Italy

    Mauro Racaniello, Alessio Cardinale & Daniela Merlo

  2. Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy

    Mauro Racaniello, Margherita D’Antuono & Virginia Tancredi

  3. Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy

    Cristiana Mollinari, Giovanna De Chiara & Daniela Merlo

Authors
  1. Mauro Racaniello
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  2. Alessio Cardinale
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  3. Cristiana Mollinari
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  4. Margherita D’Antuono
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  5. Giovanna De Chiara
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  6. Virginia Tancredi
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  7. Daniela Merlo
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Correspondence to Daniela Merlo.

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Racaniello, M., Cardinale, A., Mollinari, C. et al. Phosphorylation Changes of CaMKII, ERK1/2, PKB/Akt Kinases and CREB Activation During Early Long-Term Potentiation at Schaffer Collateral-CA1 Mouse Hippocampal Synapses. Neurochem Res 35, 239–246 (2010). https://doi.org/10.1007/s11064-009-0047-0

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  • DOI: https://doi.org/10.1007/s11064-009-0047-0

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