DNA-based MRI probes for specific detection of chronic exposure to amphetamine in living brains.
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.
Liu
Christina H
CH
Laboratory for Gene Transcript Targeting, Imaging and Repair, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Ren
Jia Q
JQ
Yang
Jinsheng
J
Liu
Charng-ming
CM
Mandeville
Joseph B
JB
Rosen
Bruce R
BR
Bhide
Pradeep G
PG
Yanagawa
Yuchio
Y
Liu
Philip K
PK
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003287:Contrast Media / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007276:Injections, Intraventricular / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D053768:Metal Nanoparticles; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054735:Phosphorothioate Oligonucleotides / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D000697:Central Nervous System Stimulants; D003287:Contrast Media; C483819:Fosb protein, mouse; D054735:Phosphorothioate Oligonucleotides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D004247:DNA; D000661:Amphetamine; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1