Content area

Abstract

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, and while the higher VPA dose induced a global decrease in whole brain volume, the lower dose induced 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.

Details

1009240
Title
Purkinje cell number-correlated cerebrocerebellar circuit anomaly in the valproate model of autism
Publication title
bioRxiv; Cold Spring Harbor
Publication year
2018
Publication date
Oct 3, 2018
Section
New Results
Publisher
Cold Spring Harbor Laboratory Press
Source
BioRxiv
Place of publication
Cold Spring Harbor
Country of publication
United States
University/institution
Cold Spring Harbor Laboratory Press
Publication subject
ISSN
2692-8205
Source type
Working Paper
Language of publication
English
Document type
Working Paper
Publication history
 
 
Online publication date
2018-10-03
Publication history
 
 
   First posting date
03 Oct 2018
ProQuest document ID
2115904431
Document URL
https://www.proquest.com/working-papers/purkinje-cell-number-correlated-cerebrocerebellar/docview/2115904431/se-2?accountid=208611
Copyright
�� 2018. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (���the License���). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Last updated
2019-09-20
Database
ProQuest One Academic