title: PKC-epsilon activation is required for recognition memory in the rat.
abstract: Activation of PKCɛ, 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 PKCɛ in memory is still lacking. Hence, we sought to evaluate this in rats, using short-term treatments with two PKCɛ-selective peptides, the inhibitory ɛV1-2 and the activating ψɛRACK, and the novel object recognition task (NORT). Our results show that the PKCɛ-selective activator ψɛRACK, did not have a significant effect on recognition memory. In the short time frames used, however, inhibition of PKCɛ activation with the peptide inhibitor ɛV1-2 significantly impaired recognition memory. Moreover, when we addressed at the molecular level the immediate proximal signalling events of PKCɛ activation in acutely dissected rat hippocampi, we found that ψɛRACK increased in a time-dependent manner phosphorylation of MARCKS and activation of Src, Raf, and finally ERK1/2, whereas ɛV1-2 inhibited all basal activity of this pathway. Taken together, these findings present the first direct evidence that PKCɛ activation is an essential molecular component of recognition memory and point toward the use of systemically administered PKCɛ-regulating peptides as memory study tools and putative therapeutic agents.
authors.affiliation: Center for Neurosciences, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Styliani
authors.initials: S
authors.lastname: Zisopoulou
authors.forename: Olga
authors.initials: O
authors.lastname: Asimaki
authors.forename: George
authors.initials: G
authors.lastname: Leondaritis
authors.forename: Anna
authors.initials: A
authors.lastname: Vasilaki
authors.forename: Nikos
authors.initials: N
authors.lastname: Sakellaridis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pitsikas
authors.forename: Dimitra
authors.initials: D
authors.lastname: Mangoura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D015696:Gene Products, tat / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000201:enzymology; D010766:Phosphorylation; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D048490:raf Kinases / Q000502:physiology; D019061:src-Family Kinases / Q000502:physiology
chemical_list: D015696:Gene Products, tat; D019061:src-Family Kinases; D048490:raf Kinases; D051744:Protein Kinase C-epsilon
keywords: CNS; ELAV; ERK; ERK1/2; MAPK; MEK; Mitogen-activated protein kinase kinase; PKCɛ; Rat hippocampus; Recognition memory; central nervous system; embryonic lethal abnormal vision protein; extracellular signal-regulated kinases; mitogen-activated protein kinases; ɛV1-2 peptide; ψɛRACK peptide