The Effects of Sindbis Viral Vectors on Neuronal Function

Seçil Uyaniker, Sophie J.F. van der Spek, Niels R. Reinders, Hui Xiong, Ka Wan Li, Koen Bossers, August B. Smit, Joost Verhaagen, Helmut W. Kessels*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Viral vectors are attractive tools to express genes in neurons. Transduction of neurons with a recombinant, replication-deficient Sindbis viral vector is a method of choice for studying the effects of short-term protein overexpression on neuronal function. However, to which extent Sindbis by itself may affect neurons is not fully understood. We assessed effects of neuronal transduction with a Sindbis viral vector on the transcriptome and proteome in organotypic hippocampal slice cultures, and analyzed the electrophysiological properties of individual CA1 neurons, at 24 h and 72 h after viral vector injection. Whereas Sindbis caused substantial gene expression alterations, changes at the protein level were less pronounced. Alterations in transcriptome and proteome were predominantly limited to proteins involved in mediating anti-viral innate immune responses. Sindbis transduction did not affect the intrinsic electrophysiological properties of individual neurons: the membrane potential and neuronal excitability were similar between transduced and non-transduced CA1 neurons up to 72 h after Sindbis injection. Synaptic currents also remained unchanged upon Sindbis transduction, unless slices were massively infected for 72 h. We conclude that Sindbis viral vectors at low transduction rates are suitable for studying short-term effects of a protein of interest on electrophysiological properties of neurons, but not for studies on the regulation of gene expression.

Original languageEnglish
Article number362
Pages (from-to)1-12
Number of pages12
JournalFrontiers in Cellular Neuroscience
Volume13
Issue numberAugust
DOIs
Publication statusPublished - 8 Aug 2019

Keywords

  • electrophysiology
  • hippocampus
  • proteomics
  • Sindbis viral vector
  • transcriptomics

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    Uyaniker, S., van der Spek, S. J. F., Reinders, N. R., Xiong, H., Li, K. W., Bossers, K., ... Kessels, H. W. (2019). The Effects of Sindbis Viral Vectors on Neuronal Function. Frontiers in Cellular Neuroscience, 13(August), 1-12. [362]. https://doi.org/10.3389/fncel.2019.00362