In vitro expression of N-acetyl aspartate by oligodendrocytes:: Implications for proton magnetic resonance spectroscopy signal in vivo

In vitro expression of N-acetyl aspartate by oligodendrocytes:: Implications for proton magnetic resonance spectroscopy signal in vivo
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DOI:
10.1046/j.1471-4159.2000.0740254.x
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发表时间:
2000-01-01
影响因子:
4.7
通讯作者:
Pearce, D
Pearce, D
中科院分区:
医学2区
文献类型:
--
作者:
Bhakoo, KK;Pearce, D

文献摘要

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磁共振波谱(MRS)提供了一种非侵入性的方法来评估体内组织的生物化学,N-乙酰天冬氨酸(NAA)是一种主要的脑代谢产物,其存在越来越多地用于临床和实验MRS研究作为一个假定的神经元标记物。通过体内H-1 MRS评估的NAA水平的降低已被认为是神经元活力的指示。然而,脑病理学的时间观察,如多发性硬化症,线粒体脑病与乳酸性酸中毒和中风样发作(MELAS),甲状腺功能减退症已显示可逆性NAA水平,可能反映神经元功能的恢复。NAA的细胞定位的知识是至关重要的,在解释这些发现。假设NAA是特定的神经元是基于以前的免疫组织化学研究全脑使用NAA特异性抗体。通过细胞培养实验进一步证实了神经元定位,在细胞培养实验中观察到其存在于少突胶质细胞2型星形胶质细胞祖细胞和未成熟的少突胶质细胞中,但不在成熟的少突胶质细胞中。最近,对少突胶质细胞生物学的研究揭示了需要营养因子来促进少突胶质细胞在体外的生成、成熟和存活。在这里,我们使用这个新的信息来实现一个更相关的细胞培养程序,并证明成熟的少突胶质细胞可以在体外表达NAA。这一观察结果提出了疑问,是否NAA的变化,在体内H-1 MRS临床研究中观察到的反映神经元功能单独。本实验结果支持了少突胶质细胞在体内表达NAA的假设,并对H-1 MRS观察到的NAA信号有贡献。
Magnetic resonance spectroscopy (MRS) provides a noninvasive means of assessing in vivo tissue biochemistry, N-Acetyl aspartate (NAA) is a major brain metabolite, and its presence is used increasingly in clinical and experimental MRS studies as a putative neuronal marker. A reduction in NAA levels as assessed by in vivo H-1 MRS has been suggested to be indicative of neuronal viability. However, temporal observations of brain pathologies such as multiple sclerosis, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS), and hypothyroidism have shown reversibility in NAA levels, possibly reflecting recovery of neuronal function. A knowledge of the cellular localisation of NAA is critical in interpreting these findings. The assumption that NAA is specific to neurones is based on previous immunohistochemical studies on whole brain using NAA-specific antibodies. The neuronal localisation was further substantiated by cell culture experiments in which its presence in the oligodendrocyte-type 2 astrocyte progenitors and immature oligodendrocytes, but not in the mature oligodendrocytes, was observed. More recently, studies on oligodendrocyte biology have revealed the requirement for trophic factors to promote the generation, maturation, and survival of oligodendrocytes in vitro. Here, we have used this new information to implement a more pertinent cell cultivation procedure and demonstrate that mature oligodendrocytes can express NAA in vitro. This observation brings into question whether the NAA changes observed in clinical in vivo H-1 MRS studies reflect neuronal function alone. The data presented here support the hypothesis that oligodendrocytes may express NAA in vivo and contribute to the NAA signal observed by H-1 MRS.