Branched-chain amino acids and neurotransmitter metabolism: expression of cytosolic branched-chain aminotransferase (BCATc) in the cerebellum and hippocampus.
Branched-chain amino acids and neurotransmitter metabolism: expression of cytosolic branched-chain aminotransferase (BCATc) in the cerebellum and hippocampus.
复制标题
支链氨基酸和神经递质代谢：小脑和海马中胞浆支链转氨酶（BCATc）的表达。
DOI：
10.1002/cne.20200
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Hutson,SusanM
中科院分区：
文献类型：
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作者：
Sweatt,AndrewJ;Garcia-Espinosa,MariaA;Wallin,Reidar;Hutson,SusanM
在大脑中，支链氨基酸（BCAA）的催化作用为谷氨酸和谷氨酰胺的合成提供了氮。谷氨酸是在支链氨基转移酶（BCAT）催化的反应中，通过将氨基从BCAA转移到α-酮戊二酸而形成的。BCAT有两种同工酶：细胞溶质BCATc（见于神经系统、卵巢和胎盘）和线粒体BCATm（见于除大鼠肝脏外的所有器官）。在细胞培养系统中，BCATc仅在神经元和发育中的少突胶质细胞中发现，而BCATm是星形胶质细胞中的同种型。在这项研究中，我们使用免疫组织化学来检查BCATc在大鼠大脑中的分布，重点是小脑和海马的众所周知的神经结构。我们发现，BCATc只在成年大鼠大脑的神经元中表达。在小脑皮质和齿状回的颗粒细胞等海马能神经元中，BCATc定位于轴突和神经末梢。相反，在GABA能神经元如小脑浦肯野细胞和海马锥体篮状细胞中，BCATc集中在细胞体中。BCATc在这些神经递质系统中的一个共同功能可能是调节可用于作为神经递质释放或用作GABA合成前体的谷氨酸的量。在我们的研究结果中，特别引人注目的是BCATc在海马结构的苔藓纤维通路中的强表达。根据抗惊厥药物加巴喷丁的有效性讨论了这一结果，加巴喷丁是BCATc的特异性抑制剂。神经学比较杂志477：360-370，2004.© 2004 Wiley利斯公司
In the brain, catabolism of the branched‐chain amino acids (BCAAs) provides nitrogen for the synthesis of glutamate and glutamine. Glutamate is formed through transfer of an amino group from BCAA to α‐ketoglutarate in reaction catalyzed by branched‐chain aminotransferases (BCAT). There are two isozymes of BCAT: cytosolic BCATc, which is found in the nervous system, ovary, and placenta, and mitochondrial BCATm, which is found in all organs except rat liver. In cell culture systems, BCATc is found only in neurons and developing oligodendrocytes, whereas BCATm is the isoform in astroglia. In this study, we used immunohistochemistry to examine the distribution of BCATc in the rat brain, focusing on the well‐known neural architecture of the cerebellum and hippocampus. We show that BCATc is expressed only in neurons in the adult rat brain. In glutamatergic neurons such as granule cells of the cerebellar cortex and of the dentate gyrus, BCATc is localized to axons and nerve terminals. In contrast, in GABAergic neurons such as cerebellar Purkinje cells and hippocampal pyramidal basket cells, BCATc is concentrated in cell bodies. A common function for BCATc in these neurotransmitter systems may be to modulate amounts of glutamate available either for release as neurotransmitter or for use as precursor for synthesis of GABA. Particularly striking in our findings is the strong expression of BCATc in the mossy fiber pathway of the hippocampal formation. This result is discussed in light of the effectiveness of the anticonvulsant drug gabapentin, which is a specific inhibitor of BCATc. J. Comp. Neurol. 477:360–370, 2004. © 2004 Wiley‐Liss, Inc.