title: Abnormalities in brain structure and biochemistry associated with mdx mice measured by in vivo MRI and high resolution localized (1)H MRS.
abstract: Duchenne muscular dystrophy (DMD), an X-linked disorder caused by the lack of dystrophin, is characterized by the progressive wasting of skeletal muscles. To date, what is known about dystrophin function is derived from studies of dystrophin-deficient animals, with the most common model being the mdx mouse. Most studies on patients with DMD and in mdx mice have focused on skeletal muscle and the development of therapies to reverse, or at least slow, the severe muscle wasting and progressive degeneration. However, dystrophin is also expressed in the CNS. Both mdx mice and patients with DMD can have cognitive and behavioral changes, but studies in the dystrophic brain are limited. We examined the brain structure and metabolites of mature wild type (WT) and mdx mice using magnetic resonance imaging and spectroscopy (MRI/MRS). Both structural and metabolic alterations were observed in the mdx brain. Enlarged lateral ventricles were detected in mdx mice when compared to WT. Diffusion tensor imaging (DTI) revealed elevations in diffusion diffusivities in the prefrontal cortex and a reduction of fractional anisotropy in the hippocampus. Metabolic changes included elevations in phosphocholine and glutathione, and a reduction in γ-aminobutyric acid in the hippocampus. In addition, an elevation in taurine was observed in the prefrontal cortex. Such findings indicate a regional structural change, altered cellular antioxidant defenses, a dysfunction of GABAergic neurotransmission, and a perturbed osmoregulation in the brain lacking dystrophin.
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Da
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Orthopaedics, School of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Stephen J P
authors.initials: SJP
authors.lastname: Pratt
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Marshall
authors.affiliation: Department of Orthopaedics, School of Medicine, University of Maryland, Baltimore, MD, USA. Electronic address: rlovering@som.umaryland.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Lovering
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D066244:Proton Magnetic Resonance Spectroscopy
keywords: DMD; Diffusion tensor imaging; Dystrophy; Magnetic resonance imaging; Magnetic resonance spectroscopy; Skeletal muscle