Ultrastructural Alterations of Myelinated Fibers and Oligodendrocytes in the Prefrontal Cortex in Schizophrenia: A Postmortem Morphometric Study

Uranova, N.A.; Vikhreva, Olga; Rachmanova, V.I.; Orlovskaya, D.D.

doi:10.1155/2011/325789

Cited by 137 publications

(121 citation statements)

References 65 publications

(63 reference statements)

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“…[42][43][44] First, postmortem studies have reported that significant reduction (14%-22%) in the density and the quantity of oligodendrocytes (cells producing myelin) [44][45][46][47][48][49][50][51][52][53][54][55][56] is seen alongside signs of apoptotic damage to myelin sheaths, 52,55,57 especially in the grey matter, and downregulation of myelin-related genes and proteins. [58][59][60][61][62][63][64] Arguably, of all the expressed brain proteins with recorded abnormalities, astrocytic and oligodendrocytic proteins appear to be the most consistently affected in patients with schizophrenia.…”

Section: The Role Of Myelin In Morphometrymentioning

confidence: 99%

The neurobiology of transition to psychosis

Palaniyappan

Das

Dempster

2017

JPN

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Section: The Role Of Myelin In Morphometrymentioning

confidence: 99%

The neurobiology of transition to psychosis

Palaniyappan

Das

Dempster

2017

JPN

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“…Reports of WM abnormalities in patients with schizophrenia are common and include reduced fractional anisotropy (FA) of water diffusion measured by diffusion tensor imaging (DTI) MRI (9-11) as well as reduced axonal myelin levels and glial cell density in postmortem brain studies (12)(13)(14). Identifying the key WM microstructural properties that explain the patient-control differences in processing speed may yield a specific quantitative target to evaluate treatments of cognitive and cerebral connectivity impairments in schizophrenia.…”

mentioning

confidence: 99%

Diffusion-weighted imaging uncovers likely sources of processing-speed deficits in schizophrenia

Kochunov

Rowland

Fieremans

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Schizophrenia, a devastating psychiatric illness with onset in the late teens to early 20s, is thought to involve disrupted brain connectivity. Functional and structural disconnections of cortical networks may underlie various cognitive deficits, including a substantial reduction in the speed of information processing in schizophrenia patients compared with controls. Myelinated white matter supports the speed of electrical signal transmission in the brain. To examine possible neuroanatomical sources of cognitive deficits, we used a comprehensive diffusion-weighted imaging (DWI) protocol and characterized the white matter diffusion signals using diffusion kurtosis imaging (DKI) and permeability-diffusivity imaging (PDI) in patients (n = 74), their nonill siblings (n = 41), and healthy controls (n = 113). Diffusion parameters that showed significant patient-control differences also explained the patient-control differences in processing speed. This association was also found for the nonill siblings of the patients. The association was specific to processing-speed abnormality but not specific to working memory abnormality or psychiatric symptoms. Our findings show that advanced diffusion MRI in white matter may capture microstructural connectivity patterns and mechanisms that govern the association between a core neurocognitive measureprocessing speed-and neurobiological deficits in schizophrenia that are detectable with in vivo brain scans. These non-Gaussian diffusion white matter metrics are promising surrogate imaging markers for modeling cognitive deficits and perhaps, guiding treatment development in schizophrenia.diffusion-weighted imaging | schizophrenia | processing speed | cognitive deficits | endophenotypes A lthough pharmaceutical interventions alleviate clinical symptoms, such as delusions and hallucinations, for some patients, schizophrenia remains a debilitating illness, often times leading to long-term disabilities and severe cognitive deficits (1). Discovering the underlying neurobiology behind these core cognitive deficits in schizophrenia patients may present a viable strategy to identify biomarkers for supporting pathophysiology and comprehensive treatment research. Two decades of research have implicated impaired brain connectivity as a source of functional disability in schizophrenia (1, 2). Delayed information processing is one of the most robust cognitive deficits (3, 4) and may contribute to other cognitive impairments in working memory and executive function (4-6).Myelinated axons in the brain's white matter (WM) support its functionality by propagating electric signal transmissions through saltatory conductance (7,8). Reports of WM abnormalities in patients with schizophrenia are common and include reduced fractional anisotropy (FA) of water diffusion measured by diffusion tensor imaging (DTI) MRI (9-11) as well as reduced axonal myelin levels and glial cell density in postmortem brain studies (12)(13)(14). Identifying the key WM microstructural properties that explain the patient-control...

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“…Malfunction of oligodendrocyte development and demyelination have been considered as a pathological substrate for cognitive dysfunction inmultiple sclerosis (MS) and schizophrenia. 1,2 Therefore, identifying and manipulating the factors regulating oligodendrocyteprecursor cells (OPCs) proliferation and differentiation are crucial to the elucidation of pathological mechanisms of demyelination diseases.…”

Section: Introductionmentioning

confidence: 99%

Cyclin-dependent kinase inhibitor flavopiridol promotes remyelination in a cuprizone induced demyelination model

Mi¹,

Gao

Liu³

et al. 2016

Cell Cycle

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The cuprizone (CPZ) model has been widely used for the studies of de-and remyelination. The CPZexposed mice show oligodendrocyte precursor cells (OPCs) increase and mature oligodendrocytes decrease, suggesting an imbalance between proliferation and differentiation of OPCs. In the first experiment of this study, we examined the expression of cell cycle related genes in brains of mice following CPZ administration for 5 weeks by means of microarray assay. In addition, we performed a double labeling of BrdU and Ki-67 to calculate cell cycle exit index in the mice. Our results showed that CPZ administration up-regulated the expression of 16 cell cycle related genes, but down-regulated the expression of only one in the prefrontal cortex (PFC) of mice compared to control group. The treatment inhibited potential precursor cells exit from cell cycle. In the second experiment, we evaluated effects of a CDK inhibitor flavopiridol (FLA) on CPZ-induced neuropathological changes and spatial working memory impairment in mice.FLA treatment for one week effectively attenuated the CPZ-induced increases in NG2 positive cells, microglia and astrocytes, alleviated the concurrent mature oligodendrocyte loss and myelin breakdown, and improved spatial working memory deficit in the CPZ-exposed mice. These results suggest that CPZ-induced neuropathological changes involve in dysregulation of cell cycle related genes. The therapeutic effects of FLA on CPZ-exposed mice may be related to its ability of cell cycle inhibition.

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Ultrastructural Alterations of Myelinated Fibers and Oligodendrocytes in the Prefrontal Cortex in Schizophrenia: A Postmortem Morphometric Study

Cited by 137 publications

References 65 publications

The neurobiology of transition to psychosis

The neurobiology of transition to psychosis

Diffusion-weighted imaging uncovers likely sources of processing-speed deficits in schizophrenia

Cyclin-dependent kinase inhibitor flavopiridol promotes remyelination in a cuprizone induced demyelination model

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