We previously reported that ganglioside GD3 is the predominant species in neural stem cells (NSCs) and reduced postnatal NSC pools are observed in both the subventricular zone and dentate gyrus (DG) of GD3-synthase knockout (GD3S-KO) mouse brains. Specifically, deficiency of GD3 in GD3S-KO animals revealed a dramatic reduction in cellularity in the DG of the hippocampus of the developing mouse brain, resulting in severe behavioral deficits in these animals. To further evaluate the functional role of GD3 in postnatal brain, we performed rescue experiments by intracerebroventricular infusion of ganglioside GD3 in adult GD3S-KO animals and found that it could restore the NSC pools and enhance the NSCs for self-renewal. Furthermore, 5xFAD mouse model was utilized, and GD3 restored NSC numbers and GM1 promoted neuronal differentiation. Our results thus demonstrate that exogenously administered gangliosides are capable to restore the function of postnatal NSCs. Since ganglioside expression profiles are associated not only with normal brain development but also with pathogenic mechanisms of diseases, such as Alzheimer’s disease, we anticipate that the administration of exogenous gangliosides, such as GD3 and GM1, may represent a novel and effective strategy for promoting adult neurogenesis in damaged brain for disease treatment.

中文翻译：

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脑室内注入神经节苷脂可增强小鼠脑中的成人神经干细胞池。

我们以前曾报道神经节苷脂GD3是神经干细胞（NSCs）中的主要物种，并且在GD3-合酶敲除（GD3S-KO）小鼠脑室的下脑区和齿状回（DG）中都观察到了出生后NSC池减少。具体而言，GD3S-KO动物中GD3的缺乏表明发育中的小鼠脑海马DG的细胞性急剧下降，从而导致这些动物严重的行为缺陷。为了进一步评估GD​​3在出生后大脑中的功能，我们通过脑室内注入神经节苷脂GD3对成年GD3S-KO动物进行了挽救实验，发现它可以恢复NSC库并增强NSC的自我更新能力。此外，利用5xFAD小鼠模型，GD3恢复了NSC数量，而GM1促进了神经元分化。因此，我们的结果表明，外源施用神经节苷脂能够恢复产后NSC的功能。由于神经节苷脂表达谱不仅与正常的大脑发育有关，而且与疾病（如阿尔茨海默氏病）的致病机制有关，因此我们预期外源神经节苷脂（如GD3和GM1）的给药可能代表了一种新的有效的成年策略。受损大脑中的神经发生，用于疾病治疗。