Decrease in N-acetylaspartate/creatine ratio in the motor area and the frontal lobe in amyotrophic lateral sclerosis

K, Abe; Takanashi, Mayako; Watanabe, Yoshiyuki; Tanaka, Hisashi; Fujita, Norihiko; Hirabuki, Norio; Yanagihara, Toshihiro

doi:10.1007/s002340000521

Cited by 53 publications

(43 citation statements)

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“…2,[16][17][18][19][20][21] Previous MRSI studies in ALS have demonstrated impaired neuronal integrity in the motor cortex, frontal lobes, and brain stem, with the findings of reduced NAA and NAA normalized to Cr or Cho (NAA/Cr, NAA/Cho). [22][23][24][25] The objective of this study was to assess in vivo neurochemical changes in the MCC and thalamus, 2 regions not previously studied with MRSI but implicated either by pathologic or imaging studies to be in- volved in ALS. Furthermore, the MCC has extensive motor connections and a large number of pyramidal neurons.…”

Section: Discussionmentioning

confidence: 99%

Degeneration of the Mid-Cingulate Cortex in Amyotrophic Lateral Sclerosis Detected In Vivo with MR Spectroscopy

Sudharshan¹,

Hanstock²,

Hui³

et al. 2010

AJNR Am J Neuroradiol

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Section: Discussionmentioning

confidence: 99%

Degeneration of the Mid-Cingulate Cortex in Amyotrophic Lateral Sclerosis Detected In Vivo with MR Spectroscopy

Sudharshan¹,

Hanstock²,

Hui³

et al. 2010

AJNR Am J Neuroradiol

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“…A number of studies have demonstrated a reduction in N-acetylaspartate (NAA), a marker of neuronal loss, in patients with ALS compared to controls expressed as absolute concentrations, 11,12 or as ratios of other metabolites like choline (Cho) and creatine (Cr) 10,[13][14][15][16][17][18][19][20][21][22][23][24] in the primary motor cortex, 13,17,19,23,25,26 centrum semiovale, internal capsule, corticospinal tract, cervical spine, 10,12,23 medulla, 5 and brainstem. Whether similar findings might be evident in people at risk for developing ALS, however, remains an unanswered question.…”

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confidence: 99%

Presymptomatic spinal cord neurometabolic findings in SOD1 -positive people at risk for familial ALS

Carew¹,

Nair²,

Andersen³

et al. 2011

Neurology

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Objective: It has been speculated that amyotrophic lateral sclerosis (ALS) is characterized by a premanifest period during which neurodegeneration precedes the appearance of clinical manifestations. Magnetic resonance spectroscopy (MRS) was used to measure ratios of neurometabolites in the cervical spine of asymptomatic individuals with a mutation in the SOD1 gene (SOD1ϩ) and compare their neurometabolic ratios to patients with ALS and healthy controls. Methods:A cross-sectional study of 1 H-MRS of the cervical spine was performed on 24 presymptomatic SOD1ϩ volunteers, 29 healthy controls, and 23 patients with ALS. All presymptomatic subjects had no symptoms of disease, normal forced vital capacity, and normal electromyographic examination. Relative concentrations of choline (Cho), creatine (Cr), myo-inositol (Myo), and N-acetylaspartate (NAA) were determined.Results: NAA/Cr and NAA/Myo ratios are reduced in both SOD1ϩ subjects (39.7%, p ϭ 0.001 and 18.0%, p ϭ 0.02) and patients with ALS (41.2%, p Ͻ 0.001 and 24.0%, p ϭ 0.01) compared to controls. Myo/Cr is reduced (10.3%, p ϭ 0.02) in SOD1ϩ subjects compared to controls, but no difference was found between patients with ALS and controls. By contrast, NAA/Cho is reduced in patients with ALS (24.0%, p ϭ 0.002), but not in presymptomatic SOD1ϩ subjects compared to controls. It has been speculated that amyotrophic lateral sclerosis (ALS) is characterized by a premanifest period during which neuronal degeneration precedes the appearance of clinical symptoms. Some evidence of this premanifest period has been derived from the superoxide dismutase (SOD1) mouse model of ALS in which there is a decline in the estimated motor unit number in advance of the appearance of symptoms. Conclusions:1 Limited data from a number of healthy individuals at risk for ALS by virtue of their carrying a mutation in the SOD1 gene (SOD1ϩ) suggest a decline in motor unit numbers several months in advance of the appearance of symptoms.

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“…In this study, we examine the metabolic and energetic effects of creatine supplementation in human brain using in vivo quantitative 1 H and 31 P spectroscopic imaging. We determine hippocampal measurements of total creatine, N-acetyl aspartate (NAA) and their spectroscopic ratio NAA/Cr.…”

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confidence: 99%

Cerebral energetic effects of creatine supplementation in humans

Pan¹,

Takahashi²

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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There has been considerable interest in the use of creatine (Cr) supplementation to treat neurological disorders. However, in contrast to muscle physiology, there are relatively few studies of creatine supplementation in the brain. In this report, we use high-field MR 31 P and 1 H spectroscopic imaging of human brain with a 7-day protocol of oral Cr supplementation to examine its effects on cerebral energetics (phosphocreatine, PCr; ATP) and mitochondrial metabolism (N-acetyl aspartate, NAA; and Cr). We find an increased ratio of PCr/ATP (day 0, 0.80 Ϯ 0.10; day 7, 0.85 Ϯ 09), with this change largely due to decreased ATP, from 2.7 Ϯ 0.3 mM to 2.5 Ϯ 0.3 mM. The ratio of NAA/Cr also decreased (day 0, 1.32 Ϯ 0.17; day 7 1.18 Ϯ 0.13), primarily from increased Cr (9.6 Ϯ 1.9 to 10.1 Ϯ 2.0 mM). The Cr-induced changes significantly correlated with the basal state, with the fractional increase in PCr/ATP negatively correlating with the basal PCr/ATP value (R ϭ Ϫ0.74, P Ͻ 0.001). As NAA is a measure of mitochondrial function, there was also a significant negative correlation between basal NAA concentrations with the fractional change in PCr and ATP. Thus healthy human brain energetics is malleable and shifts with 7 days of Cr supplementation, with the regions of initially low PCr showing the largest increments in PCr. Overall, Cr supplementation appears to improve high-energy phosphate turnover in healthy brain and can result in either a decrease or an increase in high-energy phosphate concentrations. high-energy phosphates; brain; N-acetyl aspartate; metabolism SEVERAL GROUPS HAVE SHOWN that oral creatine (Cr) supplementation can affect energy dynamics and performance in muscle (4,17,22) and brain (7,12,16,24). In both of these tissues where energy demand and ATP consumption may be temporally dynamic, relatively higher concentrations of creatine and phosphocreatine are found, presumably for its physiological role as a buffer for ATP. Also found in these tissues are mitochondrial and cytosolic creatine kinase isoforms that serve to transfer high-energy phosphate equivalents between the sites of production and consumption. Thus, as suggested in muscle (3, 18), Cr supplementation may enhance both the spatial and chemical buffering of high-energy phosphates, and this effect may contribute to the functional consequences of supplementation. For example, Watanabe et al. (24) used a double-blind placebo-controlled study of short-period creatine supplementation (5 days) to affect cognitive performance, finding that the cognitive decline associated with mental fatigue was reduced with a brief period of creatine supplementation (8 g/day for 5 days). Although these considerations have contributed to the therapeutic use of creatine in neurological diseases in which metabolic and mitochondrial dysfunction is pertinent [e.g

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Decrease in N-acetylaspartate/creatine ratio in the motor area and the frontal lobe in amyotrophic lateral sclerosis

Cited by 53 publications

References 0 publications

Degeneration of the Mid-Cingulate Cortex in Amyotrophic Lateral Sclerosis Detected In Vivo with MR Spectroscopy

Degeneration of the Mid-Cingulate Cortex in Amyotrophic Lateral Sclerosis Detected In Vivo with MR Spectroscopy

Presymptomatic spinal cord neurometabolic findings in SOD1 -positive people at risk for familial ALS

Cerebral energetic effects of creatine supplementation in humans

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