Reduced glutamate in white matter of male neonates exposed to alcohol in utero: a 1H-magnetic resonance spectroscopy study
Reduced glutamate in white matter of male neonates exposed to alcohol in utero: a 1H-magnetic resonance spectroscopy study
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DOI：
10.1007/s11011-016-9850-x
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发表时间：
2016-10-01
影响因子：
3.6
通讯作者：
Stein, D. J.
中科院分区：
文献类型：
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作者：
Howells, F. M.;Donald, K. A.;Stein, D. J.
在子宫内接触酒精会导致一系列胎儿酒精相关疾病 (FASD)。然而，很少有研究使用质子磁共振波谱 (H-1-MRS) 来了解神经化学紊乱与 FASD 病理生理学的关系。此外，迄今为止还没有研究评估在子宫内接触酒精的婴儿的大脑代谢物。我们假设，在子宫内接触酒精的新生儿会表现出谷氨酸能活性降低，从而先于其临床诊断或行为表型。单体素 H-1-MRS 数据在顶叶白质和灰质中采样，采集自 36 名在子宫内接触酒精的新生儿和 31 名未接触酒精的健康新生儿（在出生后第 2-4 周）。报告了使用磷酸肌酸相对于肌酸的代谢物和使用水参考的代谢物绝对浓度。研究发现，与健康男性婴儿相比，在子宫内接触酒精的男性婴儿的顶叶白质 (PWM) 中谷氨酸和谷氨酰胺 (Glx) 的浓度降低 (p = 0.02)。此外，与健康男性婴儿和在子宫内接触酒精的女性婴儿相比，在子宫内接触酒精的男性婴儿的 PWM 中谷氨酸 (Glu) 的浓度和比率降低 (p = 0.02)。与男婴相比，女婴顶叶灰质的相对 Glx 和 Glu 比率（PGM，p < 0.01）较高。我们推测 PWM 中 Glx 和 Glu 浓度的降低是少突胶质细胞成熟延迟的结果，这可能是在子宫内接触酒精的男性中甲状腺激素活性功能失调的结果。需要进一步的研究来阐明 Glx 和 Glu、甲状腺激素活性以及子宫内接触酒精的婴儿少突胶质细胞成熟之间的关系。
In utero exposure to alcohol leads to a spectrum of fetal alcohol related disorders (FASD). However, few studies used have used proton magnetic resonance spectroscopy (H-1-MRS) to understand how neurochemical disturbances relate to the pathophysiology of FASD. Further, no studies to date have assessed brain metabolites in infants exposed to alcohol in utero. We hypothesize that neonates exposed to alcohol in utero will show decreased glutamatergic activity, pre-emptive of their clinical diagnosis or behavioural phenotype. Single voxel H-1-MRS data, sampled in parietal white and gray matter, were acquired from 36 neonates exposed to alcohol in utero, and 31 control unexposed healthy neonates, in their 2nd-4th week of life. Metabolites relative to creatine with phosophocreatine and metabolites absolute concentrations using a water reference are reported. Male infants exposed to alcohol in utero were found to have reduced concentration of glutamate with glutamine (Glx) in their parietal white matter (PWM), compared to healthy male infants (p = 0.02). Further, male infants exposed to alcohol in utero had reduced concentration and ratio for glutamate (Glu) in their PWM (p = 0.02), compared to healthy male infants and female infants exposed to alcohol in utero. Female infants showed higher relative Glx and Glu ratios for parietal gray matter (PGM, p < 0.01), compared to male infants. We speculate that the decreased Glx and Glu concentrations in PWM are a result of delayed oligodendrocyte maturation, which may be a result of dysfunctional thyroid hormone activity in males exposed to alcohol in utero. Further study is required to elucidate the relationship between Glx and Glu, thyroid hormone activity, and oligodendrocyte maturation in infants exposure to alcohol in utero.