Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine.
Although Creatine (Cr) and Phosphocreatine (PCr) systems play a key role in cellular energy and energy transport in neuronal cells, its implications for learning and memory are still controversial. Thus, we decided to investigate the involvement of cAMP-dependent protein kinase A (PKA), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and cAMP responsive element binding protein (CREB) in the spatial consolidation after an intrahippocampal injection of Cr. Statistical analysis revealed that Cr (2.5 nmol/hippocampus) (post-training) decreased the latency for escape and the mean number of errors on Barnes maze test. Post-training co-administration of the PKA inhibitor (H-89 25 ρmol/hippocampus) did not alter the facilitatory effect of Cr in this memory test. On the other hand, Cr-induced spatial retention was reverted by co-administration of the CaMKII inhibitor (STO-609 5 nmol/hippocampus). Neurochemical analysis revealed that intrahippocampal injection of Cr, when analyzed after 30 min rather than after 3 h, increased the levels of pCREB and pCaMKII but not pPKA levels. Statistical analysis also revealed that the post-training co-administration of STO-609 but not H-89 reversed the increase of pCREB levels induced by Cr. The results presented in this report suggest that intracellular CaMKII/CREB pathway plays a key role in the Cr-induced spatial retention. Thus, it is plausible to propose that Cr plays a putative role as a neuromodulator in the brain, and that at least some of its effects may be mediated by intracellular CaMKII/CREB pathway.
Pharmacology Post Graduate Program, Physiology Department, Health Sciences Center, Federal University of Santa Maria, 97105-900, RS, Santa Maria, Brazil.
Mauren Assis
MA
Souza
Danieli Valnes
DV
Magni
Gustavo Petri
GP
Guerra
Mauro Schneider
MS
Oliveira
Ana Flávia
AF
Furian
Letícia
L
Pereira
Silvia Vacari
SV
Marquez
Juliano
J
Ferreira
Michele Rechia
MR
Fighera
Luiz Fernando Freire
LF
Royes
D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology; D050882:CREB-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003401:Creatine / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D053644:Naphthalimides / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012153:Retention, Psychology / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D053644:Naphthalimides; C458525:STO 609; D050882:CREB-Binding Protein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003401:Creatine