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Glia. 2016 Nov;64(11):2025-40. doi: 10.1002/glia.23039. Epub 2016 Jul 29.

Cortical network dysfunction caused by a subtle defect of myelination.

Author information

1
Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen.
2
Department of Radiology and Neuroradiology, Christian-Albrechts-University, Kiel.
3
Department of Functional Imaging, German Primate Center, Leibniz Institute of Primate Research, Göttingen.
4
Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen.
5
Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen. nave@em.mpg.de.
6
DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. nave@em.mpg.de.
7
Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen. ehrenreich@em.mpg.de.
8
DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. ehrenreich@em.mpg.de.

Abstract

Subtle white matter abnormalities have emerged as a hallmark of brain alterations in magnetic resonance imaging or upon autopsy of mentally ill subjects. However, it is unknown whether such reduction of white matter and myelin contributes to any disease-relevant phenotype or simply constitutes an epiphenomenon, possibly even treatment-related. Here, we have re-analyzed Mbp heterozygous mice, the unaffected parental strain of shiverer, a classical neurological mutant. Between 2 and 20 months of age, Mbp(+/-) versus Mbp(+/+) littermates were deeply phenotyped by combining extensive behavioral/cognitive testing with MRI, 1H-MR spectroscopy, electron microscopy, and molecular techniques. Surprisingly, Mbp-dependent myelination was significantly reduced in the prefrontal cortex. We also noticed a mild but progressive hypomyelination of the prefrontal corpus callosum and low-grade inflammation. While most behavioral functions were preserved, Mbp(+/-) mice exhibited defects of sensorimotor gating, as evidenced by reduced prepulse-inhibition, and a late-onset catatonia phenotype. Thus, subtle but primary abnormalities of CNS myelin can be the cause of a persistent cortical network dysfunction including catatonia, features typical of neuropsychiatric conditions. GLIA 2016;64:2025-2040.

KEYWORDS:

Cnp mutant; MRI; catatonia; electron microscopy; myelin basic protein (Mbp) mutant; prepulse inhibition

PMID:
27470661
PMCID:
PMC5129527
DOI:
10.1002/glia.23039
[Indexed for MEDLINE]
Free PMC Article

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