Magnetic resonance spectroscopy of regional brain metabolite markers in FALS mice and the effects of dietary creatine supplementation

A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
European Journal of Neuroscience (Impact Factor: 3.18). 11/2009; 30(11):2143-50. DOI: 10.1111/j.1460-9568.2009.07015.x
Source: PubMed


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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    • "T2 weighted MRI also revealed early and progressive degeneration in the trigeminal, facial and hypoglossal brain stem (Evans et al., 2014) that was replicated in human SOD1 patients who showed cortical hyperexcitability prior to symptom onset (Vucic et al., 2008). Magnetic resonance spectroscopy (MRS) has been used to demonstrate decreases in N-acetylaspartate (NAA) in the motor cortex of SOD1 G93A associated with the degree of motor dysfunction (Choi et al., 2009). Electrophysiologic measures have gained ground as a way to monitor the muscle itself. "
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    • "Glutamate is an excitatory neurotransmitter in the central nervous system and has been suggested to play a major role in ALS. Abnormalities glutamate concentrations have been identified by proton magnetic resonance spectroscopy in the brain and spinal cord of rodent FALS1 models, with changes in glutamine levels [75,76]. Increased plasma glutamate levels are observed in ALS and are correlated with longer disease duration and male gender [77]. "
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