GABA-INDUCED MOTILITY OF SPINAL NEUROBLASTS DEVELOPS ALONG A VENTRODORSAL GRADIENT AND CAN BE MIMICKED BY AGONISTS OF GABA(A) AND GABA(B) RECEPTORS
GABA-INDUCED MOTILITY OF SPINAL NEUROBLASTS DEVELOPS ALONG A VENTRODORSAL GRADIENT AND CAN BE MIMICKED BY AGONISTS OF GABA(A) AND GABA(B) RECEPTORS
复制标题
DOI：
10.1002/jnr.490420111
复制
发表时间：
1995-09-01
影响因子：
4.2
通讯作者：
BARKER, JL
中科院分区：
文献类型：
--
作者：
BEHAR, TN;SCHAFFNER, AE;BARKER, JL
在胚胎发育过程中，神经母细胞在生发区内增殖，然后迁移到它们的最终位置，尽管许多神经元沿着放射状胶质纤维迁移，但有证据表明，环境因素也影响神经母细胞的运动。在体内，神经生长因子(NGF)和γ-氨基丁酸(GABA)共同定位在迁移成神经母细胞的靶目标附近。在体外，胚胎脊髓神经元向NGF和GABA迁移(Behar等：J Neurosci 14：29-38,1994)，这意味着这两个分子在体内可能起到化学吸引剂的作用。在这里，我们使用体外迁移试验来表明，对这些吸引剂的迁移反应沿着腹背梯度发展，该梯度平行于脊髓发育过程中的终末有丝分裂，以及GABA通过涉及不同信号通路的不同受体刺激化学运动(无梯度运动)。GABA(A)(Muscimol)和GABA(B)(Baclofen)激动剂都模拟GABA刺激趋化运动的作用，Muscimol诱导的趋化运动仅被GABA(A)拮抗剂(荷包牡丹碱或印防己毒素)阻断，而向baclofen的迁移可被GABA(A)和GABA(B)(2-羟基糖芬)受体拮抗剂阻断，在8-溴cAMP或百日咳毒素存在下，向baclofen的迁移被取消，但不能被百日咳毒素抑制，表明前者而不是后者可能通过GI/GO GTP结合蛋白刺激迁移，PKA可能调节对baclofen的迁移反应每种GABA受体拮抗剂都部分减弱了向GABA的迁移，这些结果使我们得出结论，天然配体通过不同的受体耦合不同的信号机制来刺激神经母细胞的运动。(C)1995年Wiley-Liss公司
During embryogenesis, neuroblasts proliferate within germinal zones, then migrate to their final positions, Although many neurons migrate along radial glial fibers, evidence suggests that environmental factors, as yet unidentified, also influence neuroblast movement. In vivo, nerve growth factor (NGF) and gamma-aminobutyric acid (GABA) colocalize near target destinations of migratory neuroblasts, In vitro, embryonic spinal neurons migrate towards NGF and GABA (Behar et al.: J Neurosci 14:29-38, 1994), implying that the molecules may act as chemoattractants in vivo, Here, we have used an in vitro assay of migration to show that migratory responses to these attractants develop along a ventrodorsal gradient that parallels terminal mitosis during cord development, and that GABA stimulates chemokinesis (motility without a gradient) via heterogeneous receptors involving separate signalling pathways, Both GABA(A) (muscimol) and GABA(B) (baclofen) agonists mimicked the effects of GABA in stimulating chemokinesis, Muscimol-induced motility was only blocked by GABA(A) antagonists (bicuculline or picrotoxin), whereas migration to baclofen was blocked by antagonists of both GABA(A) and GABA(B) (2-hydroxysaclofen) receptors, Migration to baclofen, but not muscimol, was abolished in the presence of 8-bromo cAMP or pertussis toxin, indicating that the former, but not the latter, attractant may stimulate motility via Gi/Go GTP binding proteins, and that PKA may modulate migratory responses to baclofen, Migration to GABA was partially attenuated by each of the GABA receptor antagonists, These results lead us to conclude that the natural ligand stimulates neuroblast motility via heterogeneous receptors coupled to different signalling mechanisms. (C) 1995 Wiley-Liss, Inc.