GABA release and uptake regulate neuronal precursor migration in the postnatal subventricular zone
GABA release and uptake regulate neuronal precursor migration in the postnatal subventricular zone
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DOI：
10.1523/jneurosci.1999-04.2004
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发表时间：
2004-09-01
影响因子：
5.3
通讯作者：
Bordey, A
中科院分区：
文献类型：
--
作者：
Bolteus, AJ;Bordey, A
在出生后的室下区（SVZ），星形胶质细胞样细胞紧紧包裹着迁移神经元前体链，尽管星形胶质细胞样细胞对前体迁移的影响尚未得到证实。在急性矢状脑切片中研究细胞迁移，以确定星形胶质细胞样细胞和神经元前体之间的 GABA 信号传导是否控制幼年和成年小鼠前 SVZ 和吻部迁移流中神经元前体迁移的速度。应用 10 muM 的 GABA（GABA(A) 受体 (GABA(A)Rs) 的非脱敏浓度），通过 GABA(A)R 激活，使细胞迁移率（平均值类似于 50 mum/hr）降低了 21%。使用 GABA(A)R 拮抗剂荷包牡丹碱可将迁移率提高 30%，表明内源性 GABA 通过 GABA(A)R 激活来强效降低细胞迁移速度。使用免疫组织化学，我们发现星形胶质细胞样细胞在包裹含有 GABA 的神经元前体的过程中表达高亲和力 GABA 转运蛋白亚型 GAT4。在高 K+ 应用期间，抑制星形胶质细胞样细胞的 GABA 摄取或增强神经元前体的 GABA 释放，通过增加环境 GABA 水平进一步降低迁移率。 GABA 通过干扰细胞内 Ca2+ 信号传导而改变迁移速度，而与细胞去极化无关，因为在荷包牡丹碱存在的情况下，高 K+ 应用不会改变细胞迁移速度。这些数据表明，星形胶质细胞样细胞创造了一个微环境，其中其独特定位的 GABA 转运蛋白控制 GABA(A)R 激活程度和神经元前体的迁移。
In the postnatal subventricular zone (SVZ), astrocyte-like cells tightly encapsulate chains of migrating neuronal precursors, although an influence of the astrocyte-like cells on precursor migration has not yet been demonstrated. Cell migration was studied in acute sagittal brain slices to determine whether GABA signaling between astrocyte-like cells and neuronal precursors controls the speed of neuronal precursor migration in the anterior SVZ and rostral migratory stream of juvenile and adult mice. Application of GABA at 10 muM, a nondesensitizing concentration for GABA(A) receptors (GABA(A)Rs), reduced the rate (mean of similar to50 mum/hr) of cell migration by 21% via GABA(A)R activation. Application of the GABA(A)R antagonist bicuculline enhanced the migration rate by 30%, suggesting that endogenous GABA tonically reduces the speed of cell migration via GABA(A)R activation. Using immunohistochemistry, we found that astrocyte-like cells express the high-affinity GABA transporter subtype GAT4 on processes ensheathing neuronal precursors that contain GABA. Inhibition of GABA uptake into astrocyte-like cells or enhancement of GABA release from neuronal precursors during high K+ application further reduced the migration rate by increasing ambient GABA levels. GABA altered the migration speed by interfering with intracellular Ca2+ signaling independently of cell depolarization, because high K+ application did not alter the speed of cell migration in the presence of bicuculline. These data indicate that astrocyte-like cells create a microenvironment in which their uniquely positioned GABA transporters control the degree of GABA(A)R activation and the migration of neuronal precursors.