MRI detects therapeutic effects in weanling Niemann-Pick type C mice.
To noninvasively evaluate the early effects of Niemann-Pick type C (NPC) disease, diffusion tensor imaging (DTI) was carried out in the brains of very young (23-day-old) mice. The diffusion of water in white matter tracts of Npc1(-/-) mice at this young age was already abnormal, exhibiting decreased anisotropy, as quantified by fractional anisotropy (FA), compared with their wild-type littermates, the controls. Postmortem histological staining revealed myelin deficiencies in Npc1(-/-) mice, consistent with the reduction in FA measured in vivo. Beneficial effects of treatment with allopregnanolone and/or 2 hydroxypropyl-beta-cyclodextrin was also detectable at this age by FA, which correlated with increased myelination as seen by histology. This is the earliest detection of a therapeutic effect in Npc1(-/-) mice.
Lope-Piedrafita
Silvia
S
Biomedical Engineering Program, University of Arizona, Tucson, Arizona 85724-5073, USA.
Totenhagen
John W
JW
Hicks
Chad M
CM
Erickson
Robert P
RP
Trouard
Theodore P
TP
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D011280:Pregnanolone / Q000627:therapeutic use; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D014886:Weaning
D047908:Intracellular Signaling Peptides and Proteins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D011506:Proteins; D011280:Pregnanolone