Grey matter myelination

Timmler, Sebastian; Simons, Mikael

doi:10.1002/glia.23614

Cited by 64 publications

(60 citation statements)

References 84 publications

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“…Moreover, we found that, while the lesions showed uniform negative (Timmler and Simons, 2019). This finding is concordant with the few QSM studies that have evaluated whether iron is co-localised with myelin in deep cortical layers in healthy subjects (Deistung et al, 2013;Stüber et al, 2014).…”

Section: Measurements Of Across Cortical Depth In Groups With Well-losupporting

confidence: 91%

Quantitative MRI susceptibility mapping reveals cortical signatures of changes in iron, calcium and zinc in malformations of cortical development in children with drug-resistant epilepsy

Lorio

Sedlacik

et al. 2020

Preprint

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Objective Malformations of cortical development (MCD), including focal cortical dysplasia (FCD), are the most common cause of drug-resistant focal epilepsy in children. Histopathological lesion characterisation demonstrates abnormal cell types and lamination, alterations in myelin (typically co-localised with iron), and sometimes calcification. Quantitative susceptibility mapping (QSM) is an emerging MRI technique that measures tissue magnetic susceptibility (χ) reflecting its mineral composition. We used QSM to investigate abnormal tissue composition in a group of children with focal epilepsy with comparison to effective transverse relaxation rate (R2*) and Synchrotron radiation X-ray fluorescence (SRXRF) elemental maps. Our primary hypothesis was that reductions in χ would be found in FCD lesions, resulting from alterations in their iron and calcium content. We also evaluated deep grey matter nuclei for changes in χ with age. Methods QSM (χ) and R2* maps were calculated for 40 paediatric patients with suspected FCD (18 histologically confirmed) and 17 age-matched controls. Patients sub-groups were defined based on concordant electro-clinical or histopathology data. Quantitative investigation of QSM and R2* were performed within lesions, using a surface-based approach with comparison to homologous regions, and globally within deep brain regions using a voxel-based approach with regional values modelled with age and epilepsy as covariates. Synchrotron radiation X-ray fluorescence (SRXRF) was performed on brain tissue resected from 4 patients to map changes in iron, calcium and zinc and relate them to MRI parameters. Results Compared to fluid‐attenuated inversion recovery (FLAIR) or T1‐weighted imaging, QSM improved lesion conspicuity in 5% of patients. In patients with well-localised and confirmed FCDIIb lesions, quantitative profiling demonstrated decreased χ, but not R2*, across cortical depth with respect to the homologous regions. Contra-lateral homologous regions additionally exhibited increased χ at 2-3mm cortical depth that was absent in lesions. The iron decrease measured by the SRXRF in FCDIIb lesions was in agreement with myelin reduction observed by Luxol Fast Blue histochemical staining. SRXRF analysis in two FCDIIb tissue samples showed increased zinc and calcium, and decreased iron in the brain region exhibiting low χ and high R2*. QSM revealed expected age-related changes in the striatum nuclei, substantia nigra, sub-thalamic and red nucleus, but these changes were not altered in epilepsy. Conclusion QSM non-invasively revealed cortical/sub-cortical tissue alterations in MCD lesions and in particular that χ changes in FCDIIb lesions were consistent with reduced iron, co-localised with low myelin and increased calcium and zinc content. Theses findings suggests that the measurements of cortical χ measurements could be used to detect and delineate epilepsy lesions.

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Section: Measurements Of Across Cortical Depth In Groups With Well-losupporting

confidence: 91%

Quantitative MRI susceptibility mapping reveals cortical signatures of changes in iron, calcium and zinc in malformations of cortical development in children with drug-resistant epilepsy

Lorio

Sedlacik

et al. 2020

Preprint

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“…In humans, myelination and white matter development occur at a high rate in the first years of childhood [7], continue at a slightly slower rate during adolescence, and enter another dynamic phase in cortical areas during young adulthood [8], a vulnerable period of brain development that coincides with the average age of onset of SZ [9]. In some cortical areas, myelination contributes to lifelong brain plasticity, an adaptive process to "learning," and only reaches its maximum level after decades [10].…”

Section: Introductionmentioning

confidence: 99%

Oligodendrocytes as A New Therapeutic Target in Schizophrenia: From Histopathological Findings to Neuron-Oligodendrocyte Interaction

Raabe

Slapakova

Rossner

et al. 2019

Cells

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Imaging and postmortem studies have revealed disturbed oligodendroglia-related processes in patients with schizophrenia and provided much evidence for disturbed myelination, irregular gene expression, and altered numbers of oligodendrocytes in the brains of schizophrenia patients. Oligodendrocyte deficits in schizophrenia might be a result of failed maturation and disturbed regeneration and may underlie the cognitive deficits of the disease, which are strongly associated with impaired long-term outcome. Cognition depends on the coordinated activity of neurons and interneurons and intact connectivity. Oligodendrocyte precursors form a synaptic network with parvalbuminergic interneurons, and disturbed crosstalk between these cells may be a cellular basis of pathology in schizophrenia. However, very little is known about the exact axon-glial cellular and molecular processes that may be disturbed in schizophrenia. Until now, investigations were restricted to peripheral tissues, such as blood, correlative imaging studies, genetics, and molecular and histological analyses of postmortem brain samples. The advent of human-induced pluripotent stem cells (hiPSCs) will enable functional analysis in patient-derived living cells and holds great potential for understanding the molecular mechanisms of disturbed oligodendroglial function in schizophrenia. Targeting such mechanisms may contribute to new treatment strategies for previously treatment-resistant cognitive symptoms.

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“…AD is pathologically defined by β‐amyloid (Aβ) neuritic plaques, tau neurofibrillary tangles, and is associated with neuronal, axonal, and synaptic degeneration (Braak & Braak, ; Selkoe, ). Myelin, the insulating sheath surrounding neuronal axons, is vulnerable to AD pathology while it is essential for efficient neuronal communication by fine‐tuning conduction speed and synchronization, thereby affecting brain connectivity (Nave & Werner, ; Timmler & Simons, ). A failure in cerebral connectivity has been shown to interfere with healthy cognitive functioning (Fornito, Zalesky, & Breakspear, ; Pievani, Filippini, Van Den Heuvel, Cappa, & Frisoni, ).…”

Section: Introductionmentioning

confidence: 99%

Gray matter T1‐w/T2‐w ratios are higher in Alzheimer's disease

Pelkmans

Dicks

Barkhof

et al. 2019

Human Brain Mapping

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Myelin determines the conduction of neuronal signals along axonal connections in networks of the brain. Loss of myelin integrity in neuronal circuits might result in cognitive decline in Alzheimer's disease (AD). Recently, the ratio of T1‐weighted by T2‐weighted MRI has been used as a proxy for myelin content in gray matter of the cortex. With this approach, we investigated whether AD dementia patients show lower cortical myelin content (i.e., a lower T1‐w/T2‐w ratio value). We selected structural T1‐w and T2‐w MR images of 293 AD patients and 172 participants with normal cognition (NC). T1‐w/T2‐w ratios were computed for the whole brain and within 90 automated anatomical labeling atlas regions using SPM12, compared between groups and correlated with the neuronal injury marker tau in cerebrospinal fluid (CSF) and Mini Mental State Examination (MMSE). In contrast to our hypothesis, AD patients showed higher whole brain T1‐w/T2‐w ratios than NC, and regionally in 31 anatomical areas (p < .0005; d = 0.21 to 0.48), predominantly in the inferior parietal lobule, angular gyrus, anterior cingulate, and precuneus. Regional higher T1‐w/T2‐w values were associated with higher CSF tau concentrations (p < .0005; r = .16 to .22) and worse MMSE scores (p < .0005; r = −.16 to −.21). These higher T1‐w/T2‐w values in AD seem to contradict previous pathological findings of demyelination and disconnectivity in AD. Future research should further investigate the biological processes reflected by increases in T1‐w/T2‐w values.

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Grey matter myelination

Cited by 64 publications

References 84 publications

Quantitative MRI susceptibility mapping reveals cortical signatures of changes in iron, calcium and zinc in malformations of cortical development in children with drug-resistant epilepsy

Quantitative MRI susceptibility mapping reveals cortical signatures of changes in iron, calcium and zinc in malformations of cortical development in children with drug-resistant epilepsy

Oligodendrocytes as A New Therapeutic Target in Schizophrenia: From Histopathological Findings to Neuron-Oligodendrocyte Interaction

Gray matter T1‐w/T2‐w ratios are higher in Alzheimer's disease

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