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Cortical network dysfunction caused by a subtle defect of myelination
Author(s) -
Poggi Giulia,
Boretius Susann,
Möbius Wiebke,
Moschny Nicole,
Baudewig Jürgen,
Ruhwedel Torben,
Hassouna Imam,
Wieser Georg L.,
Werner Hauke B.,
Goebbels Sandra,
Nave KlausArmin,
Ehrenreich Hannelore
Publication year - 2016
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23039
Subject(s) - white matter , corpus callosum , neuroscience , prepulse inhibition , myelin , prefrontal cortex , oligodendrocyte , biology , pathology , psychology , magnetic resonance imaging , schizophrenia (object oriented programming) , medicine , cognition , central nervous system , psychiatry , radiology
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