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Regional and sex-dependent alterations in Purkinje cell density in the valproate mouse model of autism

Roux, Sébastiena; Bailly, Yannickb; Bossu, Jean L.a

doi: 10.1097/WNR.0000000000001164
CELLULAR, MOLECULAR AND DEVELOPMENTAL NEUROSCIENCE
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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.

aPhysiology of Neuronal Networks

bIntracellular Membrane Trafficking in Nervous and Endocrine Systems, INCI – CNRS UPR 3212, ULP, 5 rue Blaise Pascal, Strasbourg, France

Correspondence to Dr Jean L. Bossu, Physiology of Neuronal Networks, INCI, 5 rue Blaise Pascal, Strasbourg 67000, France E-mail: jlbossu@inci-cnrs.unistra.fr

Received September 14, 2018

Accepted September 30, 2018

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