Roux Sébastien, Bailly Yannick, Bossu Jean L
Physiology of Neuronal Networks.
Intracellular Membrane Trafficking in Nervous and Endocrine Systems, INCI - CNRS UPR 3212, ULP, 5 rue Blaise Pascal, Strasbourg, France.
Neuroreport. 2019 Jan 16;30(2):82-88. doi: 10.1097/WNR.0000000000001164.
Neuropathological and neuroimaging studies indicate a decrease in Purkinje cell (PC) density in the cerebellum of autistic patients and rodent models of autism. Autism is far more prevalent in males than females, and sex-specific properties of PCs have been reported recently. We investigated the differential sensitivity of PCs in the valproate acid (VPA) mouse model of autism by estimating the linear density of PCs immununolabelled with calbindin in the cerebellum of males and females. Whereas prenatal VPA treatment surprisingly increased PC linear density in both sexes 13 days after birth (P13), it significantly reduced the linear density of PCs in the cerebellum of 40-day-old (P40) males, but not females. In males, PC loss was more pronounced in the posterior part of the cerebellum and was significant in the VIth, VIIth, IXth and paramedian lobules. In females, PC loss was restricted to the paramedian lobule. These results suggest that this sex-specific sensitivity of PCs to VPA may contribute towards the motor disturbances and behavioural abnormalities observed in autism.
神经病理学和神经影像学研究表明，自闭症患者及自闭症啮齿动物模型的小脑浦肯野细胞（PC）密度降低。自闭症在男性中比女性更为普遍，最近有报道称PC具有性别特异性。我们通过估计雄性和雌性小鼠小脑内用钙结合蛋白免疫标记的PC线性密度，研究了自闭症丙戊酸（VPA）小鼠模型中PC的差异敏感性。出生后13天（P13）时，产前VPA治疗出人意料地增加了两性的PC线性密度，然而，它显著降低了40日龄（P40）雄性小鼠小脑内PC的线性密度，对雌性小鼠则无此影响。在雄性小鼠中，PC损失在小脑后部更为明显，在第六、第七、第九叶和旁正中小叶中显著。在雌性小鼠中，PC损失仅限于旁正中小叶。这些结果表明，PC对VPA的这种性别特异性敏感性可能导致自闭症中观察到的运动障碍和行为异常。
