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

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發表在:Scientific Reports (Nature Publisher Group) vol. 9 (Jun 2019), p. 1
主要作者: Spisák, Tamás
其他作者: Román, Viktor, Papp, Edit, Kedves, Rita, Sághy, Katalin, Csölle, Cecília Katalin, Varga, Anita, Gajári, Dávid, Nyitrai, Gabriella, Spisák, Zsófia, Zsigmond, Tamás Kincses, Lévay, György, Lendvai, Balázs, Czurkó, András
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024 7 |a 10.1038/s41598-019-45667-1  |2 doi 
035 |a 2246933422 
045 2 |b d20190601  |b d20190630 
084 |a 274855  |2 nlm 
100 1 |a Spisák, Tamás  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary; Department of Neurology, University Hospital Essen, Essen, Germany 
245 1 |a Purkinje cell number-correlated cerebrocerebellar circuit anomaly in the valproate model of autism 
260 |b Nature Publishing Group  |c Jun 2019 
513 |a Journal Article 
520 3 |a 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. 
653 |a Autism 
653 |a Valproic acid 
653 |a Cortex 
653 |a Information processing 
653 |a Substantia grisea 
653 |a Functional magnetic resonance imaging 
653 |a Cerebellum 
653 |a Brain stem 
653 |a Purkinje cells 
653 |a Brain mapping 
653 |a Cell number 
653 |a Environmental 
700 1 |a Román, Viktor  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary 
700 1 |a Papp, Edit  |u Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary 
700 1 |a Kedves, Rita  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary 
700 1 |a Sághy, Katalin  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary 
700 1 |a Csölle, Cecília Katalin  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary 
700 1 |a Varga, Anita  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary 
700 1 |a Gajári, Dávid  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary 
700 1 |a Nyitrai, Gabriella  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary 
700 1 |a Spisák, Zsófia  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary 
700 1 |a Zsigmond, Tamás Kincses  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary; Department of Neurology, University of Szeged, Szeged, Hungary 
700 1 |a Lévay, György  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary 
700 1 |a Lendvai, Balázs  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary 
700 1 |a Czurkó, András  |u Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary 
773 0 |t Scientific Reports (Nature Publisher Group)  |g vol. 9 (Jun 2019), p. 1 
786 0 |d ProQuest  |t Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/2246933422/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/2246933422/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch