Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6258692 | Behavioural Brain Research | 2013 | 10 Pages |
â¢The PKCÉ-selective inhibitor peptide ÉV1-2 impairs recognition memory.â¢ÏÉRACK directly activates PKCÉ in the hippocampus and sequentially Src, Raf, and ERK1/2.â¢ÉV1-2 inhibits all basal activity of the PKCÉ/Src/Raf/ERK1/2 pathway in the hippocampus.
Activation of PKCÉ, an abundant and developmentally regulated PKC isoform in the brain, has been implicated in memory throughout life and across species. Yet, direct evidence for a mechanistic role for PKCÉ in memory is still lacking. Hence, we sought to evaluate this in rats, using short-term treatments with two PKCÉ-selective peptides, the inhibitory ÉV1-2 and the activating ÏÉRACK, and the novel object recognition task (NORT). Our results show that the PKCÉ-selective activator ÏÉRACK, did not have a significant effect on recognition memory. In the short time frames used, however, inhibition of PKCÉ activation with the peptide inhibitor ÉV1-2 significantly impaired recognition memory. Moreover, when we addressed at the molecular level the immediate proximal signalling events of PKCÉ activation in acutely dissected rat hippocampi, we found that ÏÉRACK increased in a time-dependent manner phosphorylation of MARCKS and activation of Src, Raf, and finally ERK1/2, whereas ÉV1-2 inhibited all basal activity of this pathway. Taken together, these findings present the first direct evidence that PKCÉ activation is an essential molecular component of recognition memory and point toward the use of systemically administered PKCÉ-regulating peptides as memory study tools and putative therapeutic agents.