Differential excitatory vs inhibitory SCN expression at single cell level regulates brain sodium channel function in neurodevelopmental disorders

Juanjiangmeng Du, Sean Simmons, Andreas Brunklaus, Xian Adiconis, Cynthia C. Hession, Zhanyan Fu, Yinqing Li, Reut Shema, Rikke S. Møller, Boaz Barak, Guoping Feng, Miriam Meisler, Stephan Sanders, Holger Lerche, Arthur J. Campbell, Steven McCarroll, Joshua Z. Levin, Dennis Lal*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

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 SCN1A 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 E/I expression balance within cell types of sodium channels could serve as a potential strategy to develop targeted treatment for NaV-associated neuronal developmental disorders.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Paediatric Neurology
Vol/bind24
Sider (fra-til)129-133
ISSN1090-3798
DOI
StatusUdgivet - 1. jan. 2020

Fingeraftryk Dyk ned i forskningsemnerne om 'Differential excitatory vs inhibitory SCN expression at single cell level regulates brain sodium channel function in neurodevelopmental disorders'. Sammen danner de et unikt fingeraftryk.

Citationsformater