DNA-Based MRI Probes for Specific Detection of Chronic Exposure to Amphetamine in Living Brains

Article (PDF Available)inThe Journal of Neuroscience : The Official Journal of the Society for Neuroscience 29(34):10663-70 · September 2009with39 Reads
DOI: 10.1523/JNEUROSCI.2167-09.2009 · Source: PubMed
We designed phosphorothioate-modified DNA probes linked to superparamagnetic iron oxide nanoparticles (SPION) for in vivo magnetic resonance imaging (MRI) of fosB and Delta fosB mRNA after amphetamine (AMPH) exposure in mice. Specificity of both the fosB and Delta fosB probes was verified by in vitro reverse transcriptase-PCR amplification to a single fragment of total cDNA obtained from acutely AMPH-exposed mouse brains. We confirmed time-dependent uptake and retention profiles of both probes in neurons of GAD67-green fluorescent protein knock-in mice. MRI signal of SPION-labeled fosB probe delivered via intracerebroventricular route was elevated in both acutely and chronically AMPH-exposed mice; the signal was suppressed by dopaminergic receptor antagonist pretreatment. SPION-labeled Delta fosB probe signal elevation occurred only in chronically AMPH-exposed mice. The in vivo target specificity of these probes permits reliable MRI visualization of AMPH-induced differential elevations of fosB and Delta fosB mRNA in living brains.

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Available from: Philip K. Liu
    • "Although several other IEG promoters recently became popular markers of neuronal activity, the c-fos promoter is commonly used to validate findings. While the majority of imaging-based studies have focused on optical markers to monitor c-fos gene regulation , it should be noted that other means, such as magnetic resonance imaging (MRI), have been used to non-invasively monitor c-fos (Liu et al. 2007) and fosB mRNA in vivo (Liu et al. 2009). It has been suggested that genetically encoded reporters designed for MRI (Gilad et al. 2007; Bar-Shir et al. 2013), and driven by the c-fos promoter, can be applied for the real-time monitoring of gene expression in a similar manner. "
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