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脑内 GABA+与谷氨酸的关系

On the relationship between GABA+ and glutamate across the brain.

机构信息

Queensland Brain Institute, The University of Queensland, St Lucia, Australia.

School of Psychology, The University of Queensland, St Lucia, Australia.

出版信息

Neuroimage. 2022 Aug 15;257:119273. doi: 10.1016/j.neuroimage.2022.119273. Epub 2022 May 5.

DOI:10.1016/j.neuroimage.2022.119273
PMID:35526748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9924060/
Abstract

Equilibrium between excitation and inhibition (E/I balance) is key to healthy brain function. Conversely, disruption of normal E/I balance has been implicated in a range of central neurological pathologies. Magnetic resonance spectroscopy (MRS) provides a non-invasive means of quantifying in vivo concentrations of excitatory and inhibitory neurotransmitters, which could be used as diagnostic biomarkers. Using the ratio of excitatory and inhibitory neurotransmitters as an index of E/I balance is common practice in MRS work, but recent studies have shown inconsistent evidence for the validity of this proxy. This is underscored by the fact that different measures are often used in calculating E/I balance such as glutamate and Glx (glutamate and glutamine). Here we used a large MRS dataset obtained at ultra-high field (7 T) measured from 193 healthy young adults and focused on two brain regions - prefrontal and occipital cortex - to resolve this inconsistency. We find evidence that there is an inter-individual common ratio between GABA+ (γ-aminobutyric acid and macromolecules) and Glx in the occipital, but not prefrontal cortex. We further replicate the prefrontal result in a legacy dataset (n = 78) measured at high-field (3 T) strength. By contrast, with ultra-high field MRS data, we find extreme evidence that there is a common ratio between GABA+ and glutamate in both prefrontal and occipital cortices, which cannot be explained by participant demographics, signal quality, fractional tissue volume, or other metabolite concentrations. These results are consistent with previous electrophysiological and theoretical work supporting E/I balance. Our findings indicate that MRS-detected GABA+ and glutamate (but not Glx), are a reliable measure of E/I balance .

摘要

兴奋与抑制之间的平衡(E/I 平衡)是大脑健康功能的关键。相反,正常 E/I 平衡的破坏与一系列中枢神经系统疾病有关。磁共振波谱(MRS)提供了一种非侵入性的方法来量化体内兴奋性和抑制性神经递质的浓度,这些浓度可以用作诊断生物标志物。使用兴奋性和抑制性神经递质的比率作为 E/I 平衡的指标是 MRS 工作中的常见做法,但最近的研究表明,这种替代物的有效性证据并不一致。事实上,在计算 E/I 平衡时,经常使用不同的措施,例如谷氨酸和 Glx(谷氨酸和谷氨酰胺),这一点更加突出。在这里,我们使用了从 193 名健康年轻成年人获得的超高场(7 T)MRS 数据集,并集中研究了两个脑区——前额叶和枕叶——以解决这种不一致性。我们有证据表明,在枕叶而不是前额叶中,GABA+(γ-氨基丁酸和大分子)和 Glx 之间存在个体间的共同比率。我们进一步在前额叶的一个传统数据集(n=78)中复制了该结果,该数据集是在高场(3 T)强度下测量的。相比之下,使用超高场 MRS 数据,我们发现了极端的证据,表明在前额叶和枕叶中 GABA+和谷氨酸之间存在共同比率,这不能用参与者的人口统计学、信号质量、组织体积分数或其他代谢物浓度来解释。这些结果与支持 E/I 平衡的先前电生理和理论工作一致。我们的研究结果表明,MRS 检测到的 GABA+和谷氨酸(而不是 Glx)是 E/I 平衡的可靠指标。

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