Enam Alhagh Gorgich, Zahra Heidari, Hamidreza Mahmoudzadeh-Sagheb, Auob Rustamzadeh, Arash Shabani, Ali Amirzadeh, Bahram Haghi Ashtiani
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In this case-control study, 20 patients with ALS and 20 healthy controls underwent 1.5 T MRI and multivoxel <sup>1</sup>H-MRS. <sup>1</sup>H-MRS spectra to determine metabolite profiles including tNAA, mIns, tCr, tCho, and also tNAA/tCr, tNAA/tCho, and mIns/tNAA metabolite ratios from the PMC and INC were quantified via a point resolved spectroscopy pulse (PRESS) sequence in two groups. Further, the associations between <sup>1</sup>H-MRS markers with forced vital capacity (FVC), ALS functional rating scale (ALSFRS-R), and disease progression rate (ΔFS) were investigated. In the PMC, tNAA and tNAA/tCr were significantly lower in ALS patients than the healthy controls, but mIns and mIns/tNAA were significantly greater in these patients (<i>p</i> < 0.05). In the INC, tCho and mIns concentrations, and mIns/tNAA ratio were significantly increased (<i>p</i> < 0.05) in ALS patients, while tNAA and tNAA/tCr ratio did not show significant discriminations between the two groups (<i>p</i> > 0.05). The PMC tNAA/Cr ratio is associated with ALSFRS-R (<i>p</i> = 0.001, <i>r</i> = 0.71), FVC (<i>p</i> = 0.03, <i>r</i> = 0.58), and ΔFS (<i>p</i> = 0.01, <i>r</i> = -0.33). The mIns/tNAA ratio in PMC is also associated with ΔFS (<i>p</i> = 0.02, <i>r</i> = 0.41). In the INC, tCho concentrations (<i>p</i> = 0.04, <i>r</i> = -0.54) and mIns/tNAA ratio (<i>p</i> = 0.02, <i>r</i> = -0.38) were negatively associated with ALSFRS-R and positively correlated with ΔFS (<i>p</i> = 0.01, <i>r</i> = 0.33) and (<i>p</i> = 0.001, <i>r</i> = 0.61), respectively. The study suggests that neurochemistry changes in ALS patients' brains are linked to selective neuronal vulnerability and the underlying pathophysiology of the disease.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1000,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Brain Metabolite Profiles are Associated with Selective Neuronal Vulnerability and Underlying Mechanisms in Amyotrophic Lateral Sclerosis.\",\"authors\":\"Enam Alhagh Gorgich, Zahra Heidari, Hamidreza Mahmoudzadeh-Sagheb, Auob Rustamzadeh, Arash Shabani, Ali Amirzadeh, Bahram Haghi Ashtiani\",\"doi\":\"10.1021/acschemneuro.4c00593\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Amyotrophic lateral sclerosis (ALS) is a lethal neurological syndrome accompanied by selective degeneration of somatic motor neurons and neurochemistry alterations. 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In the PMC, tNAA and tNAA/tCr were significantly lower in ALS patients than the healthy controls, but mIns and mIns/tNAA were significantly greater in these patients (<i>p</i> < 0.05). In the INC, tCho and mIns concentrations, and mIns/tNAA ratio were significantly increased (<i>p</i> < 0.05) in ALS patients, while tNAA and tNAA/tCr ratio did not show significant discriminations between the two groups (<i>p</i> > 0.05). The PMC tNAA/Cr ratio is associated with ALSFRS-R (<i>p</i> = 0.001, <i>r</i> = 0.71), FVC (<i>p</i> = 0.03, <i>r</i> = 0.58), and ΔFS (<i>p</i> = 0.01, <i>r</i> = -0.33). The mIns/tNAA ratio in PMC is also associated with ΔFS (<i>p</i> = 0.02, <i>r</i> = 0.41). In the INC, tCho concentrations (<i>p</i> = 0.04, <i>r</i> = -0.54) and mIns/tNAA ratio (<i>p</i> = 0.02, <i>r</i> = -0.38) were negatively associated with ALSFRS-R and positively correlated with ΔFS (<i>p</i> = 0.01, <i>r</i> = 0.33) and (<i>p</i> = 0.001, <i>r</i> = 0.61), respectively. 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引用次数: 0
摘要
肌萎缩性侧索硬化症（ALS）是一种致命的神经系统综合征，伴有躯体运动神经元的选择性变性和神经化学改变。然而，眼动核相对来说没有受到ALS的损伤。本研究采用质子磁共振波谱（1H-MRS）技术探讨ALS患者原发性运动皮质（PMC）和Cajal间质核（INC）代谢物的变化。在这项病例对照研究中，20名ALS患者和20名健康对照者接受了1.5 T MRI和多体素1H-MRS检查。通过点分辨脉冲光谱（PRESS）序列测定两组PMC和INC代谢物谱，包括tNAA、mIns、tCr、tCho以及tNAA/tCr、tNAA/tCho和mIns/tNAA代谢物比值。此外，我们还研究了1H-MRS标志物与用力肺活量（FVC）、ALS功能评定量表（ALSFRS-R）和疾病进展率（ΔFS）之间的关系。在PMC中，ALS患者tNAA和tNAA/tCr显著低于健康对照组，而min和mIns/tNAA显著高于健康对照组（p < 0.05）。在INC中，ALS患者tCho和mIns浓度以及mIns/tNAA比值显著升高（p < 0.05），而tNAA和tNAA/tCr比值在两组间无显著差异（p < 0.05）。PMC tNAA/Cr比值与ALSFRS-R （p = 0.001, r = 0.71）、FVC （p = 0.03, r = 0.58）、ΔFS （p = 0.01, r = -0.33）相关。PMC的mIns/tNAA比值也与ΔFS相关（p = 0.02, r = 0.41）。在INC中，tCho浓度（p = 0.04, r = -0.54）和mIns/tNAA比值（p = 0.02, r = -0.38）与ALSFRS-R呈负相关，与ΔFS呈正相关（p = 0.01, r = 0.33）和（p = 0.001, r = 0.61）。该研究表明，ALS患者大脑中的神经化学变化与选择性神经元易感性和疾病的潜在病理生理有关。
Brain Metabolite Profiles are Associated with Selective Neuronal Vulnerability and Underlying Mechanisms in Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is a lethal neurological syndrome accompanied by selective degeneration of somatic motor neurons and neurochemistry alterations. Nevertheless, eye movement's nuclei are relatively spared from ALS damage. This survey was to probe metabolite changes in the primary motor cortex (PMC) and interstitial nucleus of Cajal (INC) of ALS patients using proton magnetic resonance spectroscopy (1H-MRS). In this case-control study, 20 patients with ALS and 20 healthy controls underwent 1.5 T MRI and multivoxel 1H-MRS. 1H-MRS spectra to determine metabolite profiles including tNAA, mIns, tCr, tCho, and also tNAA/tCr, tNAA/tCho, and mIns/tNAA metabolite ratios from the PMC and INC were quantified via a point resolved spectroscopy pulse (PRESS) sequence in two groups. Further, the associations between 1H-MRS markers with forced vital capacity (FVC), ALS functional rating scale (ALSFRS-R), and disease progression rate (ΔFS) were investigated. In the PMC, tNAA and tNAA/tCr were significantly lower in ALS patients than the healthy controls, but mIns and mIns/tNAA were significantly greater in these patients (p < 0.05). In the INC, tCho and mIns concentrations, and mIns/tNAA ratio were significantly increased (p < 0.05) in ALS patients, while tNAA and tNAA/tCr ratio did not show significant discriminations between the two groups (p > 0.05). The PMC tNAA/Cr ratio is associated with ALSFRS-R (p = 0.001, r = 0.71), FVC (p = 0.03, r = 0.58), and ΔFS (p = 0.01, r = -0.33). The mIns/tNAA ratio in PMC is also associated with ΔFS (p = 0.02, r = 0.41). In the INC, tCho concentrations (p = 0.04, r = -0.54) and mIns/tNAA ratio (p = 0.02, r = -0.38) were negatively associated with ALSFRS-R and positively correlated with ΔFS (p = 0.01, r = 0.33) and (p = 0.001, r = 0.61), respectively. The study suggests that neurochemistry changes in ALS patients' brains are linked to selective neuronal vulnerability and the underlying pathophysiology of the disease.
期刊介绍：
ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following:
Neurotransmitters and receptors
Neuropharmaceuticals and therapeutics
Neural development—Plasticity, and degeneration
Chemical, physical, and computational methods in neuroscience
Neuronal diseases—basis, detection, and treatment
Mechanism of aging, learning, memory and behavior
Pain and sensory processing
Neurotoxins
Neuroscience-inspired bioengineering
Development of methods in chemical neurobiology
Neuroimaging agents and technologies
Animal models for central nervous system diseases
Behavioral research
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