Neurotrophin‐3 Controls Proliferation of Granular Precursors as Well as Survival of Mature Granule Neurons in the Developing Rat Cerbellum
Neurotrophin‐3 Controls Proliferation of Granular Precursors as Well as Survival of Mature Granule Neurons in the Developing Rat Cerbellum
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Neurotropin-3 控制发育中的大鼠小脑中颗粒前体的增殖以及成熟颗粒神经元的存活
DOI：
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发表时间：
2000
影响因子：
4.7
通讯作者：
Kanefusa Kato
中科院分区：
文献类型：
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作者：
R. Katoh‐Semba;I. Takeuchi;R. Semba;Kanefusa Kato
摘要：大鼠出生后10天，小脑中神经营养因子- 3水平显著下降，提示其在早期发育过程中具有重要意义。为了进一步研究神经营养因子- 3对发育中的小脑的影响，我们将抗神经营养因子- 3的单克隆抗体注射到7.5天龄大鼠的侧脑室。由此导致的神经营养因子- 3的消耗导致小脑湿重在7天和23天后显著下降。注射抗神经营养因子- 3单克隆抗体48小时后观察到的其他变化包括：外生发层颗粒神经元中溴脱氧尿苷的结合减少，刚迁移到浦肯野细胞层下的萎缩神经元密度升高，内颗粒细胞层中凋亡神经元数量增加。这些变化仅限于中央叶。在9.5天和30天大的大鼠中，包括中央叶在内的后脑区域的神经营养因子- 3蛋白浓度分别比小脑前脑区域高4倍和3倍。免疫细胞化学检查显示，中央叶的神经营养因子- 3蛋白含量高于前叶。我们的研究结果证明，神经营养因子- 3调节颗粒前体的增殖，并支持限制性小叶中成熟颗粒神经元的存活，这表明在大鼠小脑发育的特定阶段，神经营养因子- 3参与了有限的区域。
Abstract: Levels of neurotrophin‐3 markedly decrease in the rat cerebellum after the first 10 days of life, suggesting an importance during early development. To further examine the effect of neurotrophin‐3 on the developing cerebellum, we injected a monoclonal antibody against neurotrophin‐3 into the lateral ventricle of 7.5‐day‐old rats. The resultant depletion of neurotrophin‐3 caused a significant decrease in cerebellar wet weights noted at 7 and 23 days thereafter. Other changes noted 48 h after injection of monoclonal antibodies against neurotrophin‐3 included reduced incorporation of bromodeoxyuridine into granule neurons in the external germinal layer, an elevated density of atrophic neurons that had just migrated under the Purkinje cell layer, and an increased number of apoptotic neurons in the internal granule cell layer. These changes were limited to the central lobe. The concentration of neurotrophin‐3 protein in the posterior region, including the central lobe, was about four‐ and threefold higher than that in the anterior region of the cerebellum of 9.5‐ and 30‐day‐old rats, respectively. Immunocytochemical examination showed higher amounts of neurotrophin‐3 protein in the central lobe than in the anterior lobe. Our results provide evidence that neurotrophin‐3 regulates the proliferation of granule precursors and supports the survival of mature granule neurons in restricted lobules, suggesting an involvement in limited regions at a specific stage in development of the rat cerebellum.