Effects of γ-aminobutyric acidA receptor manipulation on migrating gonadotropin-releasing hormone neurons through the entire migratory route in vivo and in vitro
Effects of γ-aminobutyric acidA receptor manipulation on migrating gonadotropin-releasing hormone neurons through the entire migratory route in vivo and in vitro
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DOI：
10.1210/en.141.3.1254
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发表时间：
2000-03-01
期刊：
影响因子：
4.8
通讯作者：
Tobet, SA
中科院分区：
文献类型：
--
作者：
Bless, EP;Westaway, WA;Tobet, SA
GnRH 神经元起源于鼻腔，沿着犁鼻纤维穿过筛板迁移到前脑。此前，我们发现在发育过程中 GnRH 神经元中存在 γ-氨基丁酸 (GABA)。为了阐明 GABA 对整个 GnRH 迁移途径的影响，我们在体内和体外检查了蝇蕈醇和荷包牡丹碱（GABA(A) 激动剂和拮抗剂）维持鼻前脑连接完整性的作用。对于体内实验，小鼠在怀孕第 10-15 天被给予蝇蕈醇、荷包牡丹碱或媒介物，并在胚胎第 15 天 (E15) 处死。对于体外实验，将 E13 小鼠整个头部的 250-μm 矢状切片与蝇蕈醇、荷包牡丹碱或载体一起孵育 2 天。蝇蕈醇抑制 GnRH 细胞迁移并减少 GnRH 纤维的延伸。荷包牡丹碱治疗导致前脑中 GnRH 细胞分布混乱，并伴随 GnRH 细胞从引导纤维中解离。这些结果表明，随着细胞移出鼻腔并向正中隆起延伸，GABA 对 GnRH 发育的影响会发生变化。
GnRH neurons originate in the nasal compartment and migrate along vomeronasal fibers over the cribiform plate to the forebrain. Previously, we found gamma-aminobutyric acid (GABA) present in GnRH neurons during development. To clarify the influence of GABA across the entire GnRH migration route, we examined the effects of muscimol and bicuculline (GABA(A) agonist and antagonist) in vivo and in vitro, maintaining the integrity of the nasal-forebrain connection. For in vivo experiments, mice were administered muscimol, bicuculline, or vehicle on days 10-15 of pregnancy and were killed on embryonic day 15 (E15). For in vitro experiments, 250-mu m parasagittal slices of whole heads of E13 mice were incubated with muscimol, bicuculline, or vehicle for 2 days. Muscimol inhibited GnRH cell migration and decreased extension of GnRH fibers. Bicuculline treatment led to a disorganized distribution of GnRH cells in the forebrain and a concomitant dissociation of GnRH cells from fibers of guidance. These results suggest that GABA's influence on GnRH development changes as the cells move out of the nasal compartment and extend processes toward the median eminence.