Chronic dietary creatine enhances hippocampal-dependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB
Open accessAbstract
The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial learning and memory in the Morris water maze and oxygen consumption rates from isolated mitochondria in real time. Levels of transcription factors and related proteins (CREB, Egr1, and IκB to indicate NF-κB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2), and mitochondrial proteins (electron transport chain Complex I, mitochondrial fission protein Drp1) were probed with Western blotting. Dietary Cr decreased escape latency/time to locate the platform ( P < 0.05) and increased the time spent in the target quadrant ( P < 0.01) in the Morris water maze. This was accompanied by increased coupled respiration ( P < 0.05) in isolated hippocampal mitochondria. Protein levels of CaMKII, PSD-95, and Complex 1 were increased in Cr-fed mice, whereas IκB was decreased. These data demonstrate that dietary supplementation with Cr can improve learning, memory, and mitochondrial function and have important implications for the treatment of diseases affecting memory and energy homeostasis.
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Snow et al found that 4 weeks of creatine supplementation in mice increased coupled respiration in isolated hippocampal mitochondria and improved memory.
“More recently, Snow et al16 found that 4 weeks of creatine supplementation in mice increased coupled respiration in isolated hippocampal mitochondria and improved memory.”
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 [16]
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References 91 · Cited by 31
- Authors
- Snow, W. M., Cadonic, C., Cortes-Perez, C., Roy Chowdhury, S. K., Djordjevic, J., Thomson, E., Bernstein, M. J., Suh, M., Fernyhough, P., & Albensi, B. C.
- Affiliations
- St. Boniface Hospital (CA)
- Pennsylvania State University (US)
- University of Manitoba (CA)
- ORCID
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2018-01-16
- Volume
- 25
- Issue
- 2
- Pages
- 54-66
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- PMC
- PMC5772392
- OpenAlex
- W2783343143
- Cited by
- 31
- References
- 91
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 2
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Learning & Memory (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Natural Sciences and Engineering Research Council (RGPIN/04742-2014)
- St. Boniface Hospital Research Foundation (1406-3216, 1403-3131, 1410-3216)
- Research Manitoba
- Alzheimer's Society of Manitoba
- University of Manitoba's Centre on Aging
- Children's Hospital Research Institute of Manitoba
- Honorable Douglas Everett, Patricia Everett
- Royal Canadian Properties Endowment
- Manitoba Dementia Research
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- hippocampus, spatial memory, spatial learning, mitochondrial bioenergetics, coupled respiration, CaMKII, PSD-95, EGR1, CREB, IκB, NF-κB, mitochondrial complex I, Drp1, mitochondrial fission, brain energy metabolism
- MeSH terms
- Animals, Creatine, Energy Metabolism, Hippocampus, Male, Mice, Inbred C57BL, Mitochondria, Neuronal Plasticity, Oxygen, Random Allocation, NF-kappa B, Maze Learning, Dietary Supplements, Spatial Memory
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