Quetiapine alleviates the cuprizone-induced white matter pathology in the brain of C57BL/6 mouse

ZHANG, Y; Xu, Haiyun; Jiang, Wen; Xiao, Lan; Yan, Bin; He, Jue; WANG, Y; Bi, Xiaoying; LI, X; Kong, Jiming

doi:10.1016/j.schres.2008.09.013

Cited by 110 publications

(92 citation statements)

References 40 publications

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“…In line with the LFB findings and previous studies [23] , MBP staining also demonstrated that CPZ treatment induced a prominent reduction in the CC of all CPZ-treated mice ( Fig. 2A, d-f), indicating CPZ-induced demyelination.…”

Section: Loss Of Mbp and Mature Oligodendrocytes Contributed To Cpz-isupporting

confidence: 92%

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Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit

Wang

et al. 2013

Neurosci. Bull.

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Schizophrenia is a mental disease that mainly affects young individuals (15 to 35 years old) but its etiology remains largely undefined. Recently, accumulating evidence indicated that demyelination and/or dysfunction of oligodendrocytes is an important feature of its pathogenesis. We hypothesized that the vulnerability of young individuals to demyelination may contribute to the onset of schizophrenia. In the present study, three different age cohorts of mice, i.e. juvenile (3 weeks), young-adult (6 weeks) and middle-aged (8 months), were subjected to a 6-week diet containing 0.2% cuprizone (CPZ) to create an animal model of acute demyelination. Then, age-related vulnerability to CPZ-induced demyelination, behavioral outcomes, and myelination-related molecular biological changes were assessed. We demonstrated: (1) CPZ treatment led to more severe demyelination in juvenile and young-adult mice than in middle-aged mice in the corpus callosum, a region closely associated with the pathophysiology of schizophrenia; (2) the higher levels of demyelination in juvenile and young-adult mice were correlated with a greater reduction of myelin basic protein, more loss of CC-1-positive mature oligodendrocytes, and higher levels of astrocyte activation; and (3) CPZ treatment resulted in a more prominent exploratory behavior deficit in juvenile and young-adult mice than in middle-aged mice. Together, our data demonstrate an age-related vulnerability to demyelination with a concurrent behavioral deficit, providing supporting evidence for better understanding the susceptibility of the young to the onset of schizophrenia.

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Section: Loss Of Mbp and Mature Oligodendrocytes Contributed To Cpz-isupporting

confidence: 92%

“…The exploratory activity has been linked with both anxiety and schizophrenia phenotypes [23,39] . Here, we demonstrated that CPZ-induced demyelination led to a deficit in exploratory activity, and juvenile mice showed the most severe deficit.…”

Section: Discussionmentioning

confidence: 99%

Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit

Wang

et al. 2013

Neurosci. Bull.

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“…Administration of the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 to rodents induces gliosis, which can be attenuated by pretreatment with the atypical antipsychotic clozapine, but not with the typical antipsychotic haloperidol (Arif et al, 2007). Consistent with this, the atypical antipsychotic quetiapine prevents astrogliosis in mice treated with the neurotoxic copper chelator, cuprizone (Zhang et al, 2008). These studies support a neuroprotective or anti-gliotic effect of atypical antipsychotic medications in vivo.…”

Section: Discussionmentioning

confidence: 73%

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Catts

Wong

Fillman

et al. 2014

Aust N Z J Psychiatry

121

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Objective: While schizophrenia may have a progressive component, the evidence for neurodegenerative processes as indicated by reactive astrocytes is inconclusive. We recently identified a subgroup of individuals with schizophrenia with increased expression of inflammatory markers in prefrontal cortex, and hypothesized that this subgroup would also have reactive astrocytes. Method:We measured glial fibrillary acidic protein (GFAP) mRNA by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) and protein levels by immunoblotting in grey matter homogenate from 37 individuals with schizophrenia and 37 unaffected controls. We examined the morphology of GFAP-positive astrocytes in immunostained sections of middle frontal gyrus. We tested if GFAP expression or astrocyte morphology were altered in people with schizophrenia with increased expression of inflammatory markers. We used RNA-Seq data on a subset of patients and controls (n=20/group) to ascertain whether mRNA transcripts associated with astrogliosis were elevated in the individuals with active neuroinflammation.Results: GFAP (mRNA and protein) levels and astrocyte morphology were not significantly different between people with schizophrenia and controls overall. However, individuals with schizophrenia with neuroinflammation had increased expression of GFAP mRNA (t(33)=2.978, p=0.005), hypertrophic astrocyte morphology (χ 2 (2)=6.281, p=0.043), and statistically significant elevated expression of three mRNA transcripts previously associated with astrogliosis. Conclusions:We found clear evidence of astrogliosis in a subset of people with schizophrenia. We suggest that the lack of astrogliosis reported in previous studies may be due to cohort differences in aetiopathology, illness stage, treatment exposure, or a failure to examine subsets of people with schizophrenia.

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“…If this is a possible mechanism of action for chronic antidepressant treatment, drug development could focus on oligodendrocytes as a therapeutic target. Recent studies have reported that quetiapine, an atypical antipsychotic approved for depression treatment, promotes both the proliferation of the NS/PCs and maturation of oligodendrocytes in cell cultures as well as in a demyelination animal model Zhang et al, 2008). Chronic administration of quetiapine has also shown efficacy as an effective monotherapy for MDD in clinical trials (Cutler et al, 2009;Weisler et al, 2009).…”

Section: May Be Mediated Through Oligodendrocytesmentioning

confidence: 99%

Hyperforin promotes mitochondrial function and development of oligodendrocytes

Wang

Zhang

et al. 2011

Journal of Neurochemistry

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Major depressive disorder is a common severe psychiatric disorder with unknown etiology. Recent studies show that the loss and malfunction of oligodendrocytes are closely related to the neuropathological changes in depression, which can be reversed by antidepressant treatment. St. John's wort is an effective and safe herbal treatment for depression in several clinical trials. However, the underlying mechanism of its therapeutic effects is unclear. In this study, we evaluated the effects of hyperforin, a iii ACKNOWLEDGEMENTS

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Quetiapine alleviates the cuprizone-induced white matter pathology in the brain of C57BL/6 mouse

Cited by 110 publications

References 40 publications

Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit

Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Hyperforin promotes mitochondrial function and development of oligodendrocytes

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