Magnetic resonance spectroscopy of regional brain metabolite markers in FALS mice and the effects of dietary creatine supplementation
Open accessAbstract
We investigated the effects of disease progression on brain regional neurochemistry in a mutant mouse model of familial amyotrophic lateral sclerosis (FALS; the G93A model) using in vivo and in vitro magnetic resonance spectroscopy (MRS). There were numerous changes in the brain spectra that were brain region dependent. At early time points starting around 80 days of age there were increases in brain glutamate. At later time points there were more extensive changes including decreased N‐acetyl aspartate and glutamate and increased glutamine, taurine and myo‐inositol. The effects of the disease were most severe in spinal cord followed by medulla and then sensorimotor cortex. There were no changes noted in cerebellum as a control region. The effects of creatine supplementation in the diet (2%) were measured in wild‐type and FALS animals in medulla, cerebellum and cortex. The increase in brain creatine was largest in cerebellum (25%) followed by medulla (11%) and then cortex (4%), reflecting the ordering of creatine kinase activity. There was a protective effect of creatine on N‐acetyl aspartate loss in the medulla at late stages. Creatine supplementation had a positive effect on weight retention, leading to a 13% increase in weight between 120 and 130 days. MRS shows promise in monitoring multiple facets of neuroprotective strategies in ALS and ALS models.
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CrM loading or low-dose long-term intake increases brain creatine content by 5-15%.
“and brain creatine content by 5–15% [72,73,74,75,76,77].”
From Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review (2022) · cites this paper as [72]
The Results section reports that a 2% creatine diet increased brain creatine by about 11% in the medulla of mice, which falls within the claimed range. It also reports an increase of about 25% in the cerebellum and no significant increase in the cortex, so this source does not support 5–15% as a general brain-wide range or establish the claim for loading or low-dose intake. (LLM, conf=0.88)
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- Authors
- Choi, J., Küstermann, E., Dedeoglu, A., & Jenkins, B. G.
- Affiliations
- Harvard University (US)
- Boston University (US)
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2009-11-30
- Volume
- 30
- Issue
- 11
- Pages
- 2143-2150
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC2846694
- OpenAlex
- W2007298590
- Cited by
- 46
- References
- 4
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 1 · 2016: 4 · 2015: 5 · 2014: 2 · 2013: 2 · 2012: 6
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- ALS Association
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R21NS059644)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- familial ALS, brain metabolites, creatine supplementation, N-acetylaspartate, glutamate, creatine kinase, medulla, cerebellum, spinal cord, neuroprotection, disease progression
- MeSH terms
- Amyotrophic Lateral Sclerosis, Animals, Aspartic Acid, Brain, Creatine, Disease Models, Animal, Glutamine, Inositol, Mice, Transgenic, Magnetic Resonance Spectroscopy, Protons, Spectrum Analysis, Superoxide Dismutase, Biomarkers, Linear Models, Glutamic Acid, Mice, In Vitro Techniques
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