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Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Astrocytic hypertrophy in dysmyelination influences the diffusion anisotropy of white matter
Laura A Harsan1, Patrick Poulet, Blandine Guignard
1UMR 7004 CNRS/ULP, Institut de Physique Biologique, Strasbourg, France.
Abstract:
The effect of a proteolipid protein (PLP) mutation on the developing white matter anisotropy was examined by diffusion tensor magnetic resonance imaging (DT-MRI) in a noninvasive study of a mouse model of Pelizaeus-Merzbacher disease (PMD). The jimpy PLP mutation in mice produces an irreversible dysmyelination in jimpy males, whereas heterozygous females exhibit a transient hypomyelination, as assessed by a longitudinal study of the same mice during development. Modifications of the different individual DT-MRI parameters were highlighted by specific changes in tissue structures caused by the mutation that includes the hypomyelination, axonal abnormalities, and recovery. Astrocytic hypertrophy is a striking cellular event in dysmyelinated jimpy brain, where most axons or bundles of fibers are entirely wrapped by astrocyte cytoplasmic processes, so its influences on DT-MRI parameters in dysmyelination were examined for the first time. DT-MRI data of the jimpy brain were compared with those obtained from dysmyelination of (oligo-TTK) transgenic mice, induced by oligodendrocyte killing, which have a mild astrocyte hypertrophy (Jalabi et al., 2005), and from recovering jimpy females, which have reduced astrocyte hypertrophy. The unique morphological feature of astrocytes in jimpy males coupled with an increase in the water channel protein aquaporin 4 (AQP4) was found to facilitate the directional water diffusion in the white matter. In addition to the major changes of DT-MRI parameters in the two dysmyelinated mice caused by the myelin loss and axonal modifications, the amplified magnitude of radial and axial diffusions in jimpy males was attributed principally to the strongly pronounced astrocyte hypertrophy.
Insights
Proteolipid protein (PLP) mutations impact white matter development in mice. Astrocytic hypertrophy in jimpy males significantly alters diffusion tensor imaging parameters, revealing new insights into Pelizaeus-Merzbacher disease.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Pelizaeus-Merzbacher disease (PMD) is a rare, inherited neurological disorder caused by mutations in the proteolipid protein (PLP) gene.
- PLP mutations lead to dysmyelination or hypomyelination in the central nervous system, affecting white matter development and function.
- Astrocytic hypertrophy, an increase in astrocyte size and number, is a prominent feature in the brains of affected individuals and animal models.
Purpose of the Study:
- To investigate the effects of a PLP mutation on white matter anisotropy during development using diffusion tensor magnetic resonance imaging (DT-MRI).
- To examine the influence of astrocytic hypertrophy on DT-MRI parameters in a mouse model of PMD.
- To compare DT-MRI findings in jimpy mice with other models of dysmyelination and recovering mice.
Main Methods:
- Noninvasive diffusion tensor magnetic resonance imaging (DT-MRI) was employed in a longitudinal study of jimpy mice (a model for PMD) and control groups.
- DT-MRI parameters, including fractional anisotropy, radial diffusivity, and axial diffusivity, were analyzed to assess white matter microstructure.
- Tissue structures, including myelin, axons, and astrocytes, were examined in correlation with DT-MRI findings.
Main Results:
- The PLP mutation in jimpy males caused irreversible dysmyelination, while heterozygous females showed transient hypomyelination.
- Significant modifications in DT-MRI parameters were observed, correlating with hypomyelination, axonal abnormalities, and recovery.
- Strongly pronounced astrocytic hypertrophy in jimpy males, along with increased aquaporin 4 (AQP4), facilitated directional water diffusion and amplified radial and axial diffusions.
Conclusions:
- Astrocytic hypertrophy plays a crucial role in altering white matter DT-MRI parameters in dysmyelination, particularly in the jimpy mouse model.
- DT-MRI can detect microstructural changes in white matter associated with PLP mutations and astrogliosis.
- Understanding these changes provides valuable insights into the pathophysiology of PMD and potential therapeutic targets.
