Sex-dimorphic effects of biogenesis of lysosome-related organelles complex-1 deficiency on mouse perinatal brain development.,Journal of Neuroscience Research

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Sex-dimorphic effects of biogenesis of lysosome-related organelles complex-1 deficiency on mouse perinatal brain development.
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2020-05-20 , DOI: 10.1002/jnr.24620
Frank Y Lee ₁ , Jennifer Larimore ₂ , Victor Faundez ₃ , Esteban C Dell'Angelica ₁ , Cristina A Ghiani _{4,

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Affiliation

The function(s) of the Biogenesis of Lysosome‐related Organelles Complex‐1 (BLOC‐1) during brain development is to date largely unknown. Here, we investigated how its absence alters the trajectory of postnatal brain development using as model the pallid mouse. Most of the defects observed early postnatally in the mutant mice were more prominent in males than in females and in the hippocampus. Male mutant mice, but not females, had smaller brains as compared to sex‐matching wild types at postnatal day 1 (P1), this deficit was largely recovered by P14 and P45. An abnormal cytoarchitecture of the pyramidal cell layer of the hippocampus was observed in P1 pallid male, but not female, or juvenile mice (P45), along with severely decreased expression levels of the radial glial marker Glutamate‐Aspartate Transporter. Transcriptomic analyses showed that the overall response to the lack of functional BLOC‐1 was more pronounced in hippocampi at P1 than at P45 or in the cerebral cortex. These observations suggest that absence of BLOC‐1 renders males more susceptible to perinatal brain maldevelopment and although most abnormalities appear to have been resolved in juvenile animals, still permanent defects may be present, resulting in faulty neuronal circuits, and contribute to previously reported cognitive and behavioral phenotypes in adult BLOC‐1‐deficient mice.

中文翻译：

溶酶体相关细胞器复合物1缺乏对小鼠围产期大脑发育的生物发生的性别二态效应。

迄今为止，溶酶体相关细胞器复合物-1 (BLOC-1) 在大脑发育过程中的生物发生功能在很大程度上是未知的。在这里，我们以苍白的老鼠为模型，研究了它的缺失如何改变出生后大脑发育的轨迹。在突变小鼠出生后早期观察到的大多数缺陷在雄性中比在雌性和海马中更为突出。与出生后第 1 天（P1）性别匹配的野生型相比，雄性突变小鼠的大脑更小，而雌性突变小鼠的大脑更小，这种缺陷在 P14 和 P45 中大部分恢复。在 P1 苍白的雄性小鼠或幼年小鼠 (P45) 中观察到海马锥体细胞层的异常细胞结构，同时放射状胶质标记物谷氨酸-天冬氨酸转运蛋白的表达水平严重下降。转录组学分析表明，对缺乏功能性 BLOC-1 的总体反应在 P1 的海马中比在 P45 或大脑皮层更明显。这些观察结果表明，缺乏 BLOC-1 会使雄性更容易受到围产期大脑发育不良的影响，尽管大多数异常似乎在幼年动物中已得到解决，但仍可能存在永久性缺陷，导致神经元回路出现故障，并有助于先前报道的认知和成年 BLOC-1 缺陷小鼠的行为表型。

更新日期：2020-05-20

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