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Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine

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Abstract

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), Ca2+/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.

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Acknowledgments

Work supported by CNPq and CAPES. Oliveira M.S. is the recipient of CNPq (research grant #150905/2009-2). Souza M.A., Magni D.V., and Guerra G.P. are recipients of CAPES. We confirm that we have read the Journal’s position on issues regarding ethical publication and affirm that this report is consistent with those guidelines. In addition, we would like to state that all authors have seen and approved the study and that no part of the work has been published or is under consideration for publication elsewhere. Moreover, the present study was supported by government funding and has no financial or other relationship that might lead to a conflict of interest. We also would like to declare that all experiments were carried out according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80–23) revised 1996, and that the University Ethics Committee approved the respective protocols.

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Authors and Affiliations

  1. Pharmacology Post Graduate Program, Physiology Department, Health Sciences Center, Federal University of Santa Maria, 97105-900, RS, Santa Maria, Brazil

    Mauren Assis Souza, Mauro Schneider Oliveira, Ana Flávia Furian, Juliano Ferreira & Luiz Fernando Freire Royes

  2. Department of Sports Methods and Techniques, Physical and Sports Education Center, Federal University of Santa Maria, Santa Maria, Brazil

    Mauren Assis Souza, Letícia Pereira, Silvia Vacari Marquez & Luiz Fernando Freire Royes

  3. Biological Sciences Post-Graduation Program: Biochemical Toxicology, Chemistry Department, Natural and Exact Sciences Center, Federal University of Santa Maria, Santa Maria, Brazil

    Danieli Valnes Magni, Gustavo Petri Guerra, Mauro Schneider Oliveira, Juliano Ferreira & Luiz Fernando Freire Royes

  4. Unipampa-campus Itaqui, Rua Luiz Joaquim de Sá Britto, 97650-000, RS, Itaqui, Brazil

    Mauro Schneider Oliveira

  5. Department of Science and Food Technology, Rural Science Center, Federal University of Santa Maria, Santa Maria, Brazil

    Ana Flávia Furian

  6. Department of Medical Clinic, Health Sciences Center, Federal University of Santa Maria, Santa Maria, Brazil

    Michele Rechia Fighera

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  1. Mauren Assis Souza
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Correspondence to Luiz Fernando Freire Royes.

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Souza, M.A., Magni, D.V., Guerra, G.P. et al. Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine. Amino Acids 43, 2491–2503 (2012). https://doi.org/10.1007/s00726-012-1329-4

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