Abnormalities in Brain and Muscle Microstructure and Neurochemistry of the DMD Rat Measured by in vivo Diffusion Tensor Imaging and High Resolution Localized 1H MRS
Date
2020-07-14Journal
Frontiers in NeurosciencePublisher
Frontiers Media S.A.Type
Article
Metadata
Show full item recordAbstract
Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by the lack of dystrophin with progressive degeneration of skeletal muscles. Most studies regarding DMD understandably focus on muscle, but dystrophin is also expressed in the central nervous system, potentially resulting in cognitive and behavioral changes. Animal models are being used for developing more comprehensive neuromonitoring protocols and clinical image acquisition procedures. The recently developed DMD rat is an animal model that parallels the progressive muscle wasting seen in DMD. Here, we studied the brain and temporalis muscle structure and neurochemistry of wild type (WT) and dystrophic (DMD) rats using magnetic resonance imaging and spectroscopy. Both structural and neurochemistry alterations were observed in the DMD rat brain and the temporalis muscle. There was a decrease in absolute brain volume (WT = 1579 mm3; DMD = 1501 mm3; p = 0.039, Cohen’s d = 1.867), but not normalized (WT = 4.27; DMD = 4.02; p = 0.306) brain volume. Diffusion tensor imaging (DTI) revealed structural alterations in the DMD temporalis muscle, with increased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). In the DMD rat thalamus, DTI revealed an increase in fractional anisotropy (FA) and a decrease in RD. Smaller normalized brain volume correlated to severity of muscle dystrophy (r = −0.975). Neurochemical changes in the DMD rat brain included increased GABA and NAA in the prefrontal cortex, and GABA in the hippocampus. Such findings could indicate disturbed motor and sensory signaling, resulting in a dysfunctional GABAergic neurotransmission, and an unstable osmoregulation in the dystrophin-null brain. © Copyright © 2020 Xu, Tang, Li, Iyer and Lovering.Sponsors
National Institute of Arthritis and Musculoskeletal and Skin DiseasesKeyword
1 H magnetic resonance spectroscopydiffusion tensor imaging
duchenne muscular dystrophy
magnetic resonance imaging
neuroimaging
rat model
Identifier to cite or link to this item
http://hdl.handle.net/10713/13535ae974a485f413a2113503eed53cd6c53
10.3389/fnins.2020.00739