Ontogeny of cation-Cl- cotransporter expression in rat neocortex
Ontogeny of cation-Cl- cotransporter expression in rat neocortex
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DOI：
10.1016/s0165-3806(98)00078-9
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发表时间：
1998-08-08
期刊：
影响因子：
--
通讯作者：
Smith, RL
中科院分区：
文献类型：
--
作者：
Clayton, GH;Owens, GC;Smith, RL
神经元前体和未成熟的皮层神经元积极积累氯-，并作为响应GABA，受体激活的结果去甲肾上腺素。随着成熟，细胞内Cl-减少，导致向GABA转移，抑制。这些观察结果表明，阳离子-Cl-cotorporters的表达的变化可能有显着的作用，在个体发育的神经元Cl-稳态。使用核糖核酸酶保护分析和原位杂交，我们研究了目前已知的所有成员的阳离子-Cl-协同转运蛋白基因家族在大鼠脑中的发育表达。在内向共转运蛋白NKCC-1、NKCC-2和NCC-1中，仅NKCC-1在脑中以显著水平检测到。NKCC-1在神经元中表达，首先出现在皮质板，而不出现在脑室或脑室下区。表达水平在出生后第三周达到峰值，并一直维持到成年。向外定向的协同转运蛋白，KCC-1和KCC-2，表现出显着不同的表达水平和时间过程。KCC-1在出生前以非常低的水平表达，在发育过程中几乎没有增加。相反，KCC-2的表达出现在围产期和出生后第一周后急剧增加。这个基因家族表达的差异变化发生在氯稳态和GABA反应的关键转变期间，暗示在这些过程中的作用。此外，缺乏表达的已知的内向cotransporters在Cl-积累的神经上皮细胞和缺乏证据的神经胶质细胞的表达表明，尚未确定的成员，这个基因家族可能参与氯稳态在不成熟的神经元前体和神经胶质细胞。(C)1998 Elsevier Science B. V.保留所有权利。
Neuronal precursors and immature cortical neurons actively accumulate Cl- and as a consequence depolarize in response to GABA, receptor activation. With maturity, intracellular Cl- decreases resulting in a shift towards GABA, inhibition. These observations suggest that changes in expression of cation-Cl- cotransporters may have a significant role in the ontogeny of neuronal Cl- homeostasis. Using ribonuclease protection analysis and in situ hybridization we examined the developmental expression of all presently known members of the cation-Cl- cotransporter gene family in rat brain. Of the inwardly directed cotransporters, NKCC-1, NKCC-2, and NCC-1, only NKCC-1 was detected at significant levels in brain. NKCC-1 was expressed in neurons, appearing first in cortical plate but not in ventricular or subventricular zone. Expression levels peaked by the third postnatal week and were maintained into adulthood. The outwardly directed cotransporters, KCC-1 and KCC-2, demonstrated significantly different levels and time courses of expression. KCC-1 was expressed prenatally at very low levels which increased little over the course of development. In contrast, KCC-2 expression appeared perinatally and increased dramatically after the first week of postnatal life. Differential changes in expression of this gene family occurred during periods of critical shifts in chloride homeostasis and GABA response suggestive of a role in these processes. Furthermore the absence of expression of known inwardly directed cotransporters in Cl- accumulating neuroepithelia and lack of evidence for glial expression suggests that as yet unidentified members of this gene family may be involved in chloride homeostasis in immature neuronal precursors and neuroglia. (C) 1998 Elsevier Science B.V. All rights reserved.