Limits...
Linking white and grey matter in schizophrenia: oligodendrocyte and neuron pathology in the prefrontal cortex.

Höistad M, Segal D, Takahashi N, Sakurai T, Buxbaum JD, Hof PR - Front Neuroanat (2009)

Bottom Line: Neuronal circuitry relies to a large extent on the presence of functional myelin produced in the brain by oligodendrocytes.The use of transgenic and mutant animal models offers a unique opportunity to analyze oligodendrocyte and neuronal changes that may have a clinical impact.Lastly, we present some recent morphological findings supporting possible causal involvement of white and grey matter abnormalities, in the aim of determining the morphologic characteristics of the circuits whose alteration leads to the cortical dysfunction that possibly underlies the pathogenesis of schizophrenia.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Mount Sinai School of Medicine New York, NY, USA.

ABSTRACT
Neuronal circuitry relies to a large extent on the presence of functional myelin produced in the brain by oligodendrocytes. Schizophrenia has been proposed to arise partly from altered brain connectivity. Brain imaging and neuropathologic studies have revealed changes in white matter and reduction in myelin content in patients with schizophrenia. In particular, alterations in the directionality and alignment of axons have been documented in schizophrenia. Moreover, the expression levels of several myelin-related genes are decreased in postmortem brains obtained from patients with schizophrenia. These findings have led to the formulation of the oligodendrocyte/myelin dysfunction hypothesis of schizophrenia. In this review, we present a brief overview of the neuropathologic findings obtained on white matter and oligodendrocyte status observed in schizophrenia patients, and relate these changes to the processes of brain maturation and myelination. We also review recent data on oligodendrocyte/myelin genes, and present some recent mouse models of myelin deficiencies. The use of transgenic and mutant animal models offers a unique opportunity to analyze oligodendrocyte and neuronal changes that may have a clinical impact. Lastly, we present some recent morphological findings supporting possible causal involvement of white and grey matter abnormalities, in the aim of determining the morphologic characteristics of the circuits whose alteration leads to the cortical dysfunction that possibly underlies the pathogenesis of schizophrenia.

No MeSH data available.


Related in: MedlinePlus

Low magnification photomicrograph of a myelin Black Gold stain of a wild-type mouse. Inset depicts the outlined cingulum bundle for analysis of fiber length density. Scale bar 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2713751&req=5

Figure 5: Low magnification photomicrograph of a myelin Black Gold stain of a wild-type mouse. Inset depicts the outlined cingulum bundle for analysis of fiber length density. Scale bar 50 μm.

Mentions: To date, two mouse models have been investigated for morphological alterations: the MAG model and the QKI model. Hof and coworkers examined two measures of white matter integrity in the MAG knockout model (Höistad et al., 2008; Segal, 2008). The cingulum bundle was examined using both DTI to examine white matter coherence as well as histological techniques to measure myelinated fiber length density. Diffusion anisotropy imaging was performed in adult MAG knockout mice, measuring the FA in a region of the cingulum bundle. At matched histological levels, using sections stained for myelin with Black Gold (Schmued and Slikker, 1999), myelinated fiber length density, defined as fiber length per unit of white matter volume was evaluated (Figure 5). The MAG knockout model displayed no alterations in either FA or fiber length density in the cingulum bundle (Segal, 2008). Thus, the effects of dysmyelination in the MAG model may be very subtle and may require ultrastructural studies to pinpoint the precise neuropathologic alterations.


Linking white and grey matter in schizophrenia: oligodendrocyte and neuron pathology in the prefrontal cortex.

Höistad M, Segal D, Takahashi N, Sakurai T, Buxbaum JD, Hof PR - Front Neuroanat (2009)

Low magnification photomicrograph of a myelin Black Gold stain of a wild-type mouse. Inset depicts the outlined cingulum bundle for analysis of fiber length density. Scale bar 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2713751&req=5

Figure 5: Low magnification photomicrograph of a myelin Black Gold stain of a wild-type mouse. Inset depicts the outlined cingulum bundle for analysis of fiber length density. Scale bar 50 μm.
Mentions: To date, two mouse models have been investigated for morphological alterations: the MAG model and the QKI model. Hof and coworkers examined two measures of white matter integrity in the MAG knockout model (Höistad et al., 2008; Segal, 2008). The cingulum bundle was examined using both DTI to examine white matter coherence as well as histological techniques to measure myelinated fiber length density. Diffusion anisotropy imaging was performed in adult MAG knockout mice, measuring the FA in a region of the cingulum bundle. At matched histological levels, using sections stained for myelin with Black Gold (Schmued and Slikker, 1999), myelinated fiber length density, defined as fiber length per unit of white matter volume was evaluated (Figure 5). The MAG knockout model displayed no alterations in either FA or fiber length density in the cingulum bundle (Segal, 2008). Thus, the effects of dysmyelination in the MAG model may be very subtle and may require ultrastructural studies to pinpoint the precise neuropathologic alterations.

Bottom Line: Neuronal circuitry relies to a large extent on the presence of functional myelin produced in the brain by oligodendrocytes.The use of transgenic and mutant animal models offers a unique opportunity to analyze oligodendrocyte and neuronal changes that may have a clinical impact.Lastly, we present some recent morphological findings supporting possible causal involvement of white and grey matter abnormalities, in the aim of determining the morphologic characteristics of the circuits whose alteration leads to the cortical dysfunction that possibly underlies the pathogenesis of schizophrenia.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Mount Sinai School of Medicine New York, NY, USA.

ABSTRACT
Neuronal circuitry relies to a large extent on the presence of functional myelin produced in the brain by oligodendrocytes. Schizophrenia has been proposed to arise partly from altered brain connectivity. Brain imaging and neuropathologic studies have revealed changes in white matter and reduction in myelin content in patients with schizophrenia. In particular, alterations in the directionality and alignment of axons have been documented in schizophrenia. Moreover, the expression levels of several myelin-related genes are decreased in postmortem brains obtained from patients with schizophrenia. These findings have led to the formulation of the oligodendrocyte/myelin dysfunction hypothesis of schizophrenia. In this review, we present a brief overview of the neuropathologic findings obtained on white matter and oligodendrocyte status observed in schizophrenia patients, and relate these changes to the processes of brain maturation and myelination. We also review recent data on oligodendrocyte/myelin genes, and present some recent mouse models of myelin deficiencies. The use of transgenic and mutant animal models offers a unique opportunity to analyze oligodendrocyte and neuronal changes that may have a clinical impact. Lastly, we present some recent morphological findings supporting possible causal involvement of white and grey matter abnormalities, in the aim of determining the morphologic characteristics of the circuits whose alteration leads to the cortical dysfunction that possibly underlies the pathogenesis of schizophrenia.

No MeSH data available.


Related in: MedlinePlus