Zhang Longbo, Huang Tianxiang, Bordey Angélique
Department of Neurosurgery, Xiangya Hospital, Central South University, 85 Xiangya Street, Changsha, 410008, China; Departments of Neurosurgery, and Cellular & Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8082, USA.
Departments of Neurosurgery, and Cellular & Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8082, USA.
Neurosci Lett. 2016 Aug 26;629:15-18. doi: 10.1016/j.neulet.2016.06.037. Epub 2016 Jun 21.
Most individuals with tuberous sclerosis complex (TSC) are born with a mutant allele of either TSC1 or TSC2 and a mosaic of psychological and cognitive defects. Tsc1 loss of heterozygosity contributes to severe dendritic abnormalities that are rescued by normalizing the levels of the actin-cross linking protein, Filamin A (FLNA). However, it is unclear whether dendrites and FLNA levels are abnormal in an heterozygote Tsc1 condition. Here, we examined dendritic morphology and FLNA levels in the olfactory bulb of Tsc1 wild type and heterozygote mice. Using in vivo neonatal electroporation to label newborn neurons followed by sholl analysis, we found that Tsc1 haploinsufficiency is associated with increased dendritic complexity and total dendritic length as well as increased FLNA levels. Since reducing FLNA levels has been shown to decrease Tsc1(+/-) dendritic complexity, these data suggest that increased FLNA levels in Tsc1(+/-) mice contribute to abnormal dendritic patterning in the Tsc1 heterozygote condition of individuals with TSC.
大多数结节性硬化症（TSC）患者出生时携带TSC1或TSC2的突变等位基因，并伴有一系列心理和认知缺陷。Tsc1杂合性缺失会导致严重的树突异常，而肌动蛋白交联蛋白细丝蛋白A（FLNA）水平的正常化可挽救这种异常。然而，目前尚不清楚在Tsc1杂合状态下树突和FLNA水平是否异常。在此，我们研究了Tsc1野生型和杂合子小鼠嗅球中的树突形态和FLNA水平。通过体内新生鼠电穿孔标记新生神经元，随后进行Sholl分析，我们发现Tsc1单倍剂量不足与树突复杂性增加、总树突长度增加以及FLNA水平升高有关。由于已证明降低FLNA水平可降低Tsc1(+/-)树突的复杂性，这些数据表明Tsc1(+/-)小鼠中FLNA水平的升高导致了TSC患者Tsc1杂合状态下树突模式异常。
