Expression of the Na-K-2Cl cotransporter is developmentally regulated in postnatal rat brains: a possible mechanism underlying GABA's excitatory role in immature brain.
Expression of the Na-K-2Cl cotransporter is developmentally regulated in postnatal rat brains: a possible mechanism underlying GABA's excitatory role in immature brain.
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DOI：
10.1002/(sici)1097-4695(19971120)33:6
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发表时间：
1997-11
期刊：
影响因子：
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通讯作者：
M. Plotkin;Evan Y. Snyder;Steven C. Hebert;Eric Delpire
中科院分区：
文献类型：
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作者：
M. Plotkin;Evan Y. Snyder;Steven C. Hebert;Eric Delpire
成熟大脑中的抑制性神经递质γ-氨基丁酸（GABA）在发育早期也表现出兴奋性。这种转变背后的机制尚不清楚。体外研究表明，钠-钾-氯共转运可能在调节未成熟神经元和少突胶质细胞对神经递质GABA的反应中发挥作用。一项体内发育研究将验证这一观点。因此，我们研究了在出生后发育的大鼠大脑中的Na-K-2Cl协同转运蛋白的BSC 2亚型的表达。通过原位杂交对发育中大鼠大脑的切片进行比较，发现了一个良好的时间和空间模式，首先增加，然后减少协同转运蛋白的表达。大脑皮层和海马中Na-K-2Cl mRNA的表达在出生后第1周最高，然后从出生后第14天（PND）到成年逐渐降低。协同转运蛋白信号在大脑、小脑的白质束中在PND 14达到峰值。在小脑祖细胞的外部颗粒层，在内部颗粒层细胞至少早在PND 7，并在浦肯野细胞在PND 14开始检测到表达。用抗BSC 2抗体和细胞类型特异性抗体对脑切片进行双标记免疫荧光证实，协同转运蛋白基因产物在白色物质的神经元和少突胶质细胞中以与原位杂交确定的模式相似的模式表达。出生后大鼠脑中Na-K-2Cl协同转运蛋白表达的时间模式支持协同转运蛋白是未成熟神经元和少突胶质细胞胞内Cl-蓄积机制的假设。
An inhibitory neurotransmitter in mature brain, gamma-aminobutyric acid (GABA) also appears to be excitatory early in development. The mechanisms underlying this shift are not well understood. In vitro studies have suggested that Na-K-Cl cotransport may have a role in modulating immature neuronal and oligodendrocyte responses to the neurotransmitter GABA. An in vivo developmental study would test this view. Therefore, we examined the expression of the BSC2 isoform of the Na-K-2Cl cotransporter in the postnatal developing rat brain. A comparison of sections from developing rat brains by in situ hybridization revealed a well-delineated temporal and spatial pattern of first increasing and then diminishing cotransporter expression. Na-K-2Cl mRNA expression in the cerebral cortex and hippocampus was highest in the first week of postnatal life and then diminished from postnatal day (PND) 14 to adult. Cotransporter signal in white-matter tracts of the cerebrum, cerebellum, peaked at PND 14. Expression was detected in cerebellar progenitor cells of the external granular layer, in internal granular layer cells at least as early as PND 7, and in Purkinje cells beginning at PND 14. Double-labeling immunofluorescence of brain sections with anti-BSC2 antibody and cell type-specific antibodies confirmed expression of the cotransporter gene product in neurons and oligodendrocytes in the white matter in a pattern similar to that determined by in situ hybridization. The temporal pattern of expression of the Na-K-2Cl cotransporter in the postnatal rat brain supports the hypothesis that the cotransporter is the mechanism of intracellular Cl- accumulation in immature neurons and oligodendrocytes.