Antisense suppression of tau in cultured rat oligodendrocytes inhibits process formation

The microtubule-associated protein tau is integral to neuronal process development and has a role in the pathogenesis of several neurodegenerative conditions. We examined possible roles for tau in cultured oligodendrocyte process formation by using antisense oligonucleotide treatment. Inhibition of tau synthesis with single oligonucleotides resulted in decreased tau protein levels and significantly shorter cellular processes. Simultaneous use of two nonoverlapping oligonucleotides caused a major reduction in tau levels and severely inhibited process outgrowth. The timing of oligonucleotide addition to oligodendrocyte cultures was important, with addition of antisense at the time of plating into culture having the most significant effect on morphology through reduction of tau expression.