Purkinje cell number-correlated cerebrocerebellar circuit anomaly in the valproate model of autism

While cerebellar alterations may play a crucial role in the development of core autism spectrum disorder (ASD) symptoms, their pathophysiology on the function of cerebrocerebellar circuit loops is largely unknown. We combined multimodal MRI (9.4 T) brain assessment of the prenatal rat valproate (VPA...

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Bibliographic Details
Main Authors: Spisák Tamás
Román Viktor
Papp Edit
Kedves Rita
Sághy Katalin
Csölle Cecília Katalin
Varga Anita
Gajári Dávid
Nyitrai Gabriella
Spisák Zsófa
Kincses Zsigmond Tamás
Lévay György István
Lendvai Balázs
Czurkó András
Format: Article
Published: 2019
Series:SCIENTIFIC REPORTS 9 No. 1
doi:10.1038/s41598-019-45667-1

mtmt:30816395
Online Access:http://publicatio.bibl.u-szeged.hu/19011
Description
Summary:While cerebellar alterations may play a crucial role in the development of core autism spectrum disorder (ASD) symptoms, their pathophysiology on the function of cerebrocerebellar circuit loops is largely unknown. We combined multimodal MRI (9.4 T) brain assessment of the prenatal rat valproate (VPA) model and correlated immunohistological analysis of the cerebellar Purkinje cell number to address this question. We hypothesized that a suitable functional MRI (fMRI) paradigm might show some altered activity related to disrupted cerebrocerebellar information processing. Two doses of maternal VPA (400 and 600 mg/kg, s.c.) were used. The higher VPA dose induced 3% smaller whole brain volume, the lower dose induced 2% smaller whole brain volume and additionally a focal gray matter density decrease in the cerebellum and brainstem. Increased cortical BOLD responses to whisker stimulation were detected in both VPA groups, but it was more pronounced and extended to cerebellar regions in the 400 mg/kg VPA group. Immunohistological analysis revealed a decreased number of Purkinje cells in both VPA groups. In a detailed analysis, we revealed that the Purkinje cell number interacts with the cerebral BOLD response distinctively in the two VPA groups that highlights atypical function of the cerebrocerebellar circuit loops with potential translational value as an ASD biomarker.
Physical Description:Azonosító: 9225-Terjedelem: 15 p
ISSN:2045-2322