Dataset Information

Cortical network dysfunction caused by a subtle defect of myelination.

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.

SUBMITTER: Poggi G

PROVIDER: S-EPMC5129527 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cortical network dysfunction caused by a subtle defect of myelination.

Poggi Giulia G Boretius Susann S Möbius Wiebke W Moschny Nicole N Baudewig Jürgen J Ruhwedel Torben T Hassouna Imam I Wieser Georg L GL Werner Hauke B HB Goebbels Sandra S Nave Klaus-Armin KA Ehrenreich Hannelore H

Glia 20160729 11

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 a ...[more]

PMID: 27470661

Similar Datasets

Project description:The synchronization of neuronal activity in the sensorimotor cortices is crucial for motor control and learning. This synchrony can be modulated by upstream activity in the cerebello-cortical network. However, many questions remain over the details of how the cerebral cortex and the cerebellum communicate. Therefore, our aim is to study the contribution of the cerebellum to oscillatory brain activity, in particular in the case of dystonia, a severely disabling motor disease associated with altered sensorimotor coupling. We used a kainic-induced dystonia model to evaluate cerebral cortical oscillatory activity and connectivity during dystonic episodes. We performed microinjections of low doses of kainic acid into the cerebellar vermis in mice and examined activities in somatosensory, motor and parietal cortices. We showed that repeated applications of kainic acid into the cerebellar vermis, for five consecutive days, generate reproducible dystonic motor behavior. No epileptiform activity was recorded on electrocorticogram (ECoG) during the dystonic postures or movements. We investigated the ECoG power spectral density and coherence between motor cortex, somatosensory and parietal cortices before and during dystonic attacks. During the baseline condition, we found a phenomenon of permanent adaptation with a change of baseline locomotor activity coupled to an ECoG gamma band increase in all cortices. In addition, after kainate administration, we observed an increase in muscular activity, but less signs of dystonia together with modulations of the ECoG power spectra with an increase in gamma band in motor, parietal and somatosensory cortices. Moreover, we found reduced coherence in all measured frequency bands between the motor cortex and somatosensory or parietal cortices compared to baseline. In conclusion, examination of cortical oscillatory activities in this animal model of chronic dystonia caused by cerebellar dysfunction reveals a disruption in the coordination of neuronal activity across the cortical sensorimotor/parietal network, which may underlie motor skill deficits.

Dataset Information

Cortical network dysfunction caused by a subtle defect of myelination.

Publications

Cortical network dysfunction caused by a subtle defect of myelination.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets