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

Souza, Mauren Assis; Magni, Danieli Valnes; Guerra, Gustavo Petri; Oliveira, Mauro Schneider; Furian, Ana Flávia; Pereira, Letícia; Marquez, Silvia Vacari; Ferreira, Juliano; Fighera, Michele Rechia; Royes, Luiz Fernando Freire

doi:10.1007/s00726-012-1329-4

Cited by 42Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

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

Souza, Mauren Assis, Magni, Danieli Valnes, Guerra, Gustavo Petri, Oliveira, Mauro Schneider, Furian, Ana Flávia, Pereira, Letícia, Marquez, Silvia Vacari, Ferreira, Juliano, Fighera, Michele Rechia, Royes, Luiz Fernando Freire·2012·Amino Acids

DOI 10.1007/s00726-012-1329-4

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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), 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.

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CREB is upregulated 30 minutes after creatine injection.
“Further, cAMP-response element binding protein (CREB), a key transcription factor involved in memory consolidation,15 is upregulated 30 minutes after creatine injection.14”
From Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [14]
In rats, intrahippocampal injections of creatine in the CA1 subfield enhances spatial memory formation.
“In rats, intrahippocampal injections of creatine in the CA1 subfield enhances spatial memory formation.14”
From Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [14]

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Authors: Souza, M. A., Magni, D. V., Guerra, G. P., Oliveira, M. S., Furian, A. F., Pereira, L., Marquez, S. V., Ferreira, J., Fighera, M. R., & Royes, L. F. F.
Affiliations: Universidade Federal de Santa Maria (BR)
Corresponding author: Royes, Luiz Fernando Freire
ORCID: Souza, Mauren Assis
Guerra, Gustavo Petri
Oliveira, Mauro Schneider
Furian, Ana Flávia
Pereira, Letícia
Ferreira, Juliano
Fighera, Michele Rechia
Royes, Luiz Fernando Freire
Venue: Amino Acids
Publisher: Springer Science and Business Media LLC
Published: 2012-06-05
Volume: 43
Issue: 6
Pages: 2491-2503
ISSN: 0939-4451 (ISSN-L)
1438-2199
DOI: 10.1007/s00726-012-1329-4
OpenAlex: W2006708261
Cited by: 42
References: 52
Citations by year: 2026: 3 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 2
FWCI: 0.98
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Amino Acids (publishedVersion)
PubMed (publishedVersion)
Funders: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: creatine, hippocampus, CaMKII, CREB, pKa, cAMP signaling, STO-609, H89, phosphocreatine, memory consolidation, neuromodulators
MeSH terms: Animals, Benzimidazoles, Creatine, Hippocampus, Male, Retention, Psychology, Structure-Activity Relationship, Signal Transduction, Rats, Wistar, Maze Learning, CREB-Binding Protein, Rats, Naphthalimides, Calcium-Calmodulin-Dependent Protein Kinase Type 2

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

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