Universität zu Köln

Du, Juanjiangmeng, Simmons, Sean, Brunklaus, Andreas, Adiconis, Xian, Hession, Cynthia C., Fu, Zhanyan, Li, Yinqing, Shema, Reut, Moller, Rikke S., Barak, Boaz, Feng, Guoping, Meisler, Miriam, Sanders, Stephan, Lerche, Holger, Campbell, Arthur J., McCarroll, Steven, Levin, Joshua Z. and Lal, Dennis (2020). Differential excitatory vs inhibitory SCN expression at single cell level regulates brain sodium channel function in neurodevelopmental disorders. Eur. J. Paediatr. Neurol., 24. S. 129 - 134. OXFORD: ELSEVIER SCI LTD. ISSN 1532-2130

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Abstract

The four voltage-gated sodium channels SCN1/2/3/8A have been associated with heterogeneous types of developmental disorders, each presenting with disease specific temporal and cell type specific gene expression. Using single-cell RNA sequencing transcriptomic data from humans and mice, we observe that SCNIA is predominantly expressed in inhibitory neurons. In contrast, SCN2/3/8A are profoundly expressed in excitatory neurons with SCN2/3A starting prenatally, followed by SCN1/8A neonatally. In contrast to previous observations from low resolution RNA screens, we observe that all four genes are expressed in both excitatory and inhibitory neurons, however, exhibit differential expression strength. These findings provide molecular evidence, at single-cell resolution, to support the hypothesis that the excitatory/inhibitory (E/I) neuronal expression ratios of sodium channels are important regulatory mechanisms underlying brain homeostasis and neurological diseases. Modulating the Ell expression balance within cell types of sodium channels could serve as a potential strategy to develop targeted treatment for Nay-associated neuronal developmental disorders. (C) 2019 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Du, Juanjiangmeng UNSPECIFIED UNSPECIFIED UNSPECIFIED Simmons, Sean UNSPECIFIED UNSPECIFIED UNSPECIFIED Brunklaus, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Adiconis, Xian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hession, Cynthia C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fu, Zhanyan UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Yinqing UNSPECIFIED UNSPECIFIED UNSPECIFIED Shema, Reut UNSPECIFIED UNSPECIFIED UNSPECIFIED Moller, Rikke S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barak, Boaz UNSPECIFIED UNSPECIFIED UNSPECIFIED Feng, Guoping UNSPECIFIED UNSPECIFIED UNSPECIFIED Meisler, Miriam UNSPECIFIED UNSPECIFIED UNSPECIFIED Sanders, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Lerche, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Campbell, Arthur J. UNSPECIFIED UNSPECIFIED UNSPECIFIED McCarroll, Steven UNSPECIFIED UNSPECIFIED UNSPECIFIED Levin, Joshua Z. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lal, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-351251
DOI:	10.1016/j.ejpn.2019.12.019
Journal or Publication Title:	Eur. J. Paediatr. Neurol.
Volume:	24
Page Range:	S. 129 - 134
Date:	2020
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1532-2130
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SEVERE MYOCLONIC EPILEPSY Multiple languages Clinical Neurology; Pediatrics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/35125