title: Evidence from the R6/2 Mouse Model of Huntington's Disease for Using Abnormal Brain Metabolism as a Biomarker for Evaluating Therapeutic Approaches for Treatment.
abstract: Huntington's disease (HD) is an autosomal dominant genetic disorder characterized by a progression of motor abnormalities as well as cognitive and psychiatric symptoms [1]. Presently, there is no cure for HD and no treatment to reverse its course or prevent its onset. HD has been characterized primarily by significant degeneration of the striatum. In addition, imaging studies have shown alterations in extra-striatal regions including the cortex [2, 3], hippocampus, and hypothalamus [4]. Although previous functional magnetic resonance imaging (fMRI) studies in patients have yielded complex and heterogeneous findings, identifying functional alterations may serve as a useful tool for tracking the progression of HD and assessing the effects of therapeutic interventions. In a recent article Cepeda-Prado et el. use novel and groundbreaking fMRI methods to elucidate functional, structural, and metabolic alterations in the R6/2 mouse model of HD. Based on changes in relative cerebral brain volume (rCBV), neuronal activity, and glucose utilization, the authors suggest that R6/2 mice have impaired neurometabolic coupling. They propose the use of rCBV as a biomarker of HD progression, providing a basis for future research examining functional alterations in animal models.
authors.affiliation: Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior and the Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Parievsky
authors.affiliation: Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior and the Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cepeda
authors.affiliation: Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior and the Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
keywords: Huntington's disease; R6/2 mouse model; [14C] 2DG uptake; functional magnetic resonance imaging; local field potentials; magnetic resonance imaging; relative cerebral blood volume; seizure