title: Structural MRI detects progressive regional brain atrophy and neuroprotective effects in N171-82Q Huntington's disease mouse model.
abstract: Huntington's disease (HD) displays progressive striatal atrophy that occurs long before the onset of clinical motor symptoms. As there is no treatment for the disease once overt symptoms appear, it has been suggested that neuroprotective therapy given during this presymptomatic period might slow progression of the disease. This requires biomarkers that can reliably detect early changes and are sensitive to treatment response. In mouse models of HD, structural MRI measures have been shown to detect disease onset. To determine whether such measures could also be suitable biomarkers for following responses to treatment, we used T2-weighted MR imaging combined with automated morphological analyses and characterized changes in regional brain volumes longitudinally in the N171-82Q HD mouse model in a preclinical trial. We report here that N171-82Q HD mice exhibit adult-onset and progressive brain atrophy in the striatum and neocortex as well as in whole brain; the progressive atrophy in striatum and neocortex is positively correlated with motor deficits. Most notably, MRI also detected neuroprotective effects of sertraline treatment, a neuroprotective agent confirmed in our previous studies. Our present studies provide the first evidence that longitudinal structural MRI measures can detect the therapeutic effect in HD mice, suggesting that such measures in brain could be valuable biomarkers in HD clinical trials.
authors.affiliation: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Qi
authors.initials: Q
authors.lastname: Peng
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Hou
authors.forename: Manisha
authors.initials: M
authors.lastname: Aggarwal
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Zhang
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Duan
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001284:Atrophy; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000473:pathology*; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006816:Huntington Disease / Q000188:drug therapy* / Q000473:pathology* / Q000523:psychology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009068:Movement / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018401:Sample Size; D016019:Survival Analysis
chemical_list: D018696:Neuroprotective Agents; D004247:DNA