Phosphothioated oligodeoxynucleotides induce nonspecific effects on neuronal cell adhesion in a growth substrate-dependent manner

Eitan Okun, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Synthetic phosphothioated (PTO) oligodeoxynucleotide (ODN) sequences are commonly used for a variety of applications that benefit from nuclease protection. The PTO modification is implemented mainly in antisense ODN, but also in ODN that were shown to activate members of the toll-like receptor (TLR) family such as TLR3 (poly-I:C), TLR8 (ssRNA), and TLR9 (CpG). Neurons are routinely plated on surfaces coated with either cationic substances such as poly-L-ornithine (PLO), polyethylenimine (PEI), poly-L-lysine or ECM components such as laminin, collagen, or fibronectin. We found that PTO-ODN aimed at activating TLR9 induces a non-TLR9-specific detachment phenotype in cortical neurons plated on either laminin or PEI, but not on PLO. This phenotype was correlated with decreased viability and was partially inhibited when caspase-3 was inhibited with Ac-DEVD-CMK. This finding suggests that the use of PTO-ODN can cause nonspecific effects on cell adhesion that could compromise interpretation of data from experiments using PTO-ODN.

Original languageEnglish (US)
Pages (from-to)1947-1952
Number of pages6
JournalJournal of Neuroscience Research
Volume87
Issue number8
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Adhesion
  • Neurons
  • ODN
  • Phosphothioate
  • Toll-like receptors

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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