Brain metabolite changes in alcoholism: An in vivo proton magnetic resonance spectroscopy (MRS) study

Jagannathan, Naranamangalam R.; Desai, Ninad; Raghunathan, P.

doi:10.1016/0730-725x(96)00048-3

Cited by 95 publications

(72 citation statements)

References 25 publications

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“…Schizophrenia-MRS is capable of detecting both endogenous compounds in the brain as well as consumed or administered drugs ranging from anti-cancer agents (Port and Wolf, 2003), to alcohol ingested in excess (Danielsen and Ross, 1999) to anti-epileptic medications (e.g., valproic acid) administered in therapeutic doses (Bluml et al, 2002). Chronic alcoholism is accompanied by loss of NAA (Jagannathan et al, 1996;Meyerhoff et al, 2004) which in some studies is reported to recover after prolonged abstinence (Parks et al, 2002).…”

Section: Magnetic Resonance Spectroscopy and Imaging Of Naamentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,229

1,126

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The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

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Section: Magnetic Resonance Spectroscopy and Imaging Of Naamentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,229

1,126

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“…An increased Cho level has been previously interpreted to represent degradation of membrane phospholipids. 7 An increased Cre level has been thought to represent glial cell proliferation. 3,6 These processes may be increased in the early stages of ALS, leading to our findings of increased Cre and Cho concentrations at the initial examination, followed by progressive decreases.…”

Section: Discussionmentioning

confidence: 99%

“…Cre represents a combination of creatine and phosphocreatine, a putative marker of gliosis, 3,6 and Cho is thought to be a marker associated with membrane phospholipids. 7 In most previous MRS studies of ALS, 4,[8][9][10][11][12][13][14][15][16][17][18][19][20] sampling of metabolite signals from the motor cortex was limited, because measurements were restricted to a rectangular region within the brain that was sufficiently distant from the skull to avoid interferences with an intense signal from extracranial lipids. Furthermore, because the selected regions of interest were generally large, including unavoidably some white matter and nonmotor tissue, results from these studies may have been skewed to the extent that white matter and nonmotor regions contributed to the metabolite signal from the motor cortex.…”

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confidence: 99%

Early detection and longitudinal changes in amyotrophic lateral sclerosis by ¹ H MRSI

Suhy

Miller²,

Rule³

et al. 2002

Neurology

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Objective-To determine 1) the reproducibility of metabolite measurements by 1 H MRS in the motor cortex; 2) the extent to which 1 H MRS imaging (MRSI) detects abnormal concentrations of N-acetylaspartate (NAA)-, choline (Cho)-, and creatine (Cre)-containing compounds in early stages of ALS; and 3) the metabolite changes over time in ALS.Methods-Sixteen patients with definite or probable ALS, 12 with possible or suspected ALS, and 12 healthy controls underwent structural MRI and multislice 1 H MRSI. 1 H MRSI data were coregistered with tissue-segmented MRI data to obtain concentrations of NAA, Cre, and Cho in the left and right motor cortex and in gray matter and white matter of nonmotor regions in the brain.Results-The interclass correlation coefficient of NAA was 0.53 in the motor cortex tissue and 0.83 in nonmotor cortex tissue. When cross-sectional data for patients were compared with those for controls, the NAA/(Cre + Cho) ratio in the motor cortex region was significantly reduced, primarily due to increases in Cre and Cho and a decrease in NAA concentrations. A similar, although not significant, trend of increased Cho and Cre and reduced NAA levels was also observed for patients with possible or suspected ALS. Furthermore, in longitudinal studies, decreases in NAA, Cre, and Cho concentrations were detected in motor cortex but not in nonmotor regions in ALS.Conclusion-Metabolite changes measured by 1 H MRSI may provide a surrogate marker of ALS that can aid detection of early disease and monitor progression and treatment response.ALS is a neurodegenerative disorder that causes rapid loss of motor neurons in the brain and spinal cord leading to paralysis and death. Diagnosis is based solely on clinical data, and there is no definitive diagnostic test for ALS and no surrogate marker for directly measuring disease progression. Therefore, an objective and quantitative method would be extremely helpful to evaluate viability and functioning of upper motor neurons in ALS, identify individuals at an early stage of the disease, and monitor responses to treatment. In addition to NAA, 1 H MRS measures resonances from choline (Cho)-and creatine (Cre)-containing compounds in the brain. Cre represents a combination of creatine and phosphocreatine, a putative marker of gliosis, 3,6 and Cho is thought to be a marker associated with membrane phospholipids. 7In most previous MRS studies of ALS,4,[8][9][10][11][12][13][14][15][16][17][18][19][20] sampling of metabolite signals from the motor cortex was limited, because measurements were restricted to a rectangular region within the brain that was sufficiently distant from the skull to avoid interferences with an intense signal from extracranial lipids. Furthermore, because the selected regions of interest were generally large, including unavoidably some white matter and nonmotor tissue, results from these studies may have been skewed to the extent that white matter and nonmotor regions contributed to the metabolite signal from the motor cortex. With use of a multiplana...

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“…In alcoholism uncomplicated by WE, MRS provides evidence for abnormally low peaks of N-acetylaspartate (NAA), a marker for mature viable neurons, or choline (Cho), an index of membrane turnover, in frontal, parietal, or cerebellar regions within a month of withdrawal (Durazzo et al, 2004;Fein et al, 1994;Jagannathan et al, 1996;Schweinsburg et al, 2003Schweinsburg et al, , 2001Seitz et al, 1999) followed by improvement in NAA or Cho, suggesting neuronal recovery (Bendszus et al, 2001;Ende et al, 2005;Martin et al, 1995;Parks et al, 2002). In WE, whether preceded by alcoholism or other precipitating condition, an early deficit in NAA can improve, more so in the thalamus than cerebellum (Murata et al, 2001), a recovery pattern noted earlier by Victor et al (1971Victor et al ( , 1989.…”

Section: Introductionmentioning

confidence: 99%

Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study

Pfefferbaum

Adalsteinsson

Bell

et al. 2006

Neuropsychopharmacol

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Wernicke's encephalopathy (WE) is characterized by lesions in thalamus, hypothalamus (including mammillary nuclei), and inferior colliculi, results in serious disabilities, has an etiology of thiamine deficiency, is treatable with thiamine, and occurs most commonly with alcoholism. Despite decades of study, whether alcohol exposure exacerbates the neuropathology or retards its resolution remains controversial. To examine patterns of brain damage and recovery resulting from thiamine deprivation with and without alcohol exposure, we conducted in vivo magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3 T in alcohol-preferring (P) rats, which had voluntarily consumed large amounts of alcohol before thiamine manipulation. A total of 18 adult male P rats (nine alcohol-exposed) received a thiamine-deficient diet for 2 weeks: 10 (five alcohol-exposed) received intraperitoneal (i.p.) pyrithiamine (PT) and eight (four alcohol-exposed) received i.p. thiamine supplementation. Neurological signs developed by day 14. Rats were scanned before thiamine depletion and 18 and 35 days after thiamine repletion. Two-dimensional J-resolved MRS single-voxel spectra with water reference were collected in a voxel subtending the thalamus; metabolite quantification was corrected for voxel tissue content. MRI identified significant enlargement of dorsal ventricles and increase in signal intensities in thalamus, inferior colliculi, and mammillary nuclei of PT compared with thiamine-treated (TT) groups from MRI 1-2, followed by significant normalization from MRI 2-3 in thalamus and colliculi, but not mammillary nuclei and lateral ventricles. Voxel-by-voxel analysis revealed additional hyperintense signal clusters in the dorsal and ventral hippocampus and enlargement of the fourth ventricle. MRS showed a significant decline and then partial recovery in thalamic N-acetylaspartate, a marker of neuronal integrity, in PT compared with TT rats, with no change detected in creatine, choline, or glutamate. PT rats with prior alcohol exposure exhibited attenuated recovery in the thalamus and arrested growth of the corpus callosum; further, two of the five alcohol-exposed PT rats died prematurely. Parenchymal and ventricular changes with thiamine manipulation concur with human radiological signs of WE. The enduring macrostructural and neurochemical abnormalities involving critical nodes of Papez circuit carry liabilities for development of amnesia and incomplete recovery from other cognitive and motor functions subserved by the affected neural systems.

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Brain metabolite changes in alcoholism: An in vivo proton magnetic resonance spectroscopy (MRS) study

Cited by 95 publications

References 25 publications

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Early detection and longitudinal changes in amyotrophic lateral sclerosis by ¹ H MRSI

Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study

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Brain metabolite changes in alcoholism: An in vivo proton magnetic resonance spectroscopy (MRS) study

Cited by 95 publications

References 25 publications

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Early detection and longitudinal changes in amyotrophic lateral sclerosis by 1 H MRSI

Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study

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Early detection and longitudinal changes in amyotrophic lateral sclerosis by ¹ H MRSI