Olanzapine ameliorates neuropathological changes and increases IGF-1 expression in frontal cortex of C57BL/6 mice exposed to cuprizone

Zhang, Handi; Zhang, Yanbo; Xu, Haiyun; Wang, Lingyan; Adilijiang, Abulimiti; Wang, Junhui; Hartle, Kelly; Zhang, Zhijun; Zhang, Dai; Tan, Qihua; Kong, Jiming; Huang, Qingjun; Li, Xinmin

doi:10.1016/j.psychres.2014.02.019

Cited by 22 publications

(12 citation statements)

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“…However, some diseases such as MS, stroke, and spinal cord injury cause degeneration of mature oligodendrocytes and induced damage of myelin sheath ( Emery, 2010 ; Zuchero and Barres, 2013 ). In CUP administrated animals that undergo demyelination, increase in OPCs and dramatic decrease in mature oligodendrocytes were observed in the corpus callosum, suggesting a blockade of OPCs differentiation into mature oligodendrocytes ( Zhang et al, 2014 ; Abulimiti et al, 2015 ), Acer truncatum oil promote remyelination by accelerated the differentiation of OPCs to mature oligodendrocytes.…”

Section: Discussionmentioning

confidence: 99%

Dietary Supplementation With Acer truncatum Oil Promotes Remyelination in a Mouse Model of Multiple Sclerosis

et al. 2022

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BackgroundMultiple sclerosis is a chronic demyelinating disease of uncertain etiology. Traditional treatment methods produce more adverse effects. Epidemiological and clinical treatment findings showed that unknown environmental factors contribute to the etiology of MS and that diet is a commonly assumed factor. Despite the huge interest in diet expressed by people with MS and the potential role diet plays in MS, very little data is available on the role of diet in MS pathogenesis and MS course, in particular, studies on fats and MS. The oil of Acer truncatum is potential as a resource to be exploited in the treatment of some neurodegenerative diseases.ObjectiveHere, we investigated the underlying influences of Acer truncatum oil on the stimulation of remyelination in a cuprizone mouse model of demyelination.MethodsCuprizone (0.2% in chow) was used to establish a mouse model of demyelination. Acer truncatum oil was administrated to mice during remyelination. Following techniques were used: behavioral test, histochemistry, fluorescent immunohistochemistry, transmission electron microscope.ResultsMice exposed to cuprizone for 6 weeks showed schizophrenia-like behavioral changes, the increased exploration of the center in the open field test (OFT), increased entries into the open arms of the elevated plus-maze, as well as demyelination in the corpus callosum. After cuprizone withdrawal, the diet therapy was initiated with supplementation of Acer truncatum oil for 2 weeks. As expected, myelin repair was greatly enhanced in the demyelinated regions with increased mature oligodendrocytes (CC1) and myelin basic protein (MBP). More importantly, the supplementation with Acer truncatum oil in the diet reduced the schizophrenia-like behavior in the open field test (OFT) and the elevated plus-maze compared to the cuprizone recovery group. The results revealed that the diet supplementation with Acer truncatum oil improved behavioral abnormalities, oligodendrocyte maturation, and remyelination in the cuprizone model during recovery.ConclusionDiet supplementation with Acer truncatum oil attenuates demyelination induced by cuprizone, indicating that Acer truncatum oil is a novel therapeutic diet in demyelinating diseases.

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Section: Discussionmentioning

confidence: 99%

Dietary Supplementation With Acer truncatum Oil Promotes Remyelination in a Mouse Model of Multiple Sclerosis

et al. 2022

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“…Finally, and in support of impaired connectivity in schizophrenia, aberrant synapse formation was found in response to microglial activation (Sargin et al ., ). With regard to white matter, several studies report that elevated microglial cells are accompanied by myelin and oligodendrocyte loss particularly in the frontal cortex (Zhang et al ., ; Morita et al ., ; Zhang et al ., ), which were reversed by the administration of the antipsychotics quetiapine (Zhang et al ., ) and olanzapine (Zhang et al ., ). The association between microglial activation, myelin and oligodendrocyte loss in these animal models may underlie connectivity impairments observed in schizophrenia (Zalesky et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Microglial activation and progressive brain changes in schizophrenia

Laskaris

Biase

Everall

et al. 2016

British J Pharmacology

191

124

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Schizophrenia is a debilitating disorder that typically begins in adolescence and is characterized by perceptual abnormalities, delusions, cognitive and behavioural disturbances and functional impairments. While current treatments can be effective, they are often insufficient to alleviate the full range of symptoms. Schizophrenia is associated with structural brain abnormalities including grey and white matter volume loss and impaired connectivity. Recent findings suggest these abnormalities follow a neuroprogressive course in the earliest stages of the illness, which may be associated with episodes of acute relapse. Neuroinflammation has been proposed as a potential mechanism underlying these brain changes, with evidence of increased density and activation of microglia, immune cells resident in the brain, at various stages of the illness. We review evidence for microglial dysfunction in schizophrenia from both neuroimaging and neuropathological data, with a specific focus on studies examining microglial activation in relation to the pathology of grey and white matter. The studies available indicate that the link between microglial dysfunction and brain change in schizophrenia remains an intriguing hypothesis worthy of further examination. Future studies in schizophrenia should: (i) use multimodal imaging to clarify this association by mapping brain changes longitudinally across illness stages in relation to microglial activation; (ii) clarify the nature of microglial dysfunction with markers specific to activation states and phenotypes; (iii) examine the role of microglia and neurons with reference to their overlapping roles in neuroinflammatory pathways; and (iv) examine the impact of novel immunomodulatory treatments on brain structure in schizophrenia. Linked Articles This article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit 10.1111/bph.2016.173.issue-4

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“…Although most work in the field has been focusing on quetiapine, one study also examined the effect of olanzapine in cuprizone-induced demyelination in mice. Here, olanzapine was found to effectively decrease myelin breakdown and loss of oligodendrocytes, in response to cuprizone exposure in mice 60 . Further studies should aim at resolving whether the olanzapine induced upregulated expression of genes linked to oligodendrocytes and myelination processes is a general effect, by comparing different antipsychotic drugs head to head.…”

Section: Discussionmentioning

confidence: 84%

Subchronic olanzapine exposure leads to increased expression of myelination-related genes in rat fronto-medial cortex

et al. 2017

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Schizophrenia is a psychotic disorder with severe and disabling symptoms, such as hallucinations, delusions, blunted affect and social withdrawal. The neuropathology remains elusive, but disturbances in immunity-related processes, neuronal connectivity and myelination have consistently been linked to schizophrenia. Antipsychotic drugs can be efficient in reducing symptoms, acting primarily on the dopamine system, but additional biological targets are likely to exist. Here we have screened for novel mechanisms of action in an animal model, using adult rats exposed to long-acting olanzapine, achieving stable and clinically relevant antipsychotic drug concentrations. By microarray-based examination of global gene expression in the fronto-medial cortex, at the single gene- and gene-set level, we observed downregulation of two neuropeptide-encoding genes, Vgf and Cort (fold change −1,25 and −1,48, respectively) in response to olanzapine exposure. Furthermore, we demonstrated significant upregulation of five out of ~2000 GO predefined gene sets after olanzapine exposure. Strikingly, all were linked to myelination and oligodendrocyte development; “Ensheathment of neurons”, “Axon ensheathment”, “Myelination”, “Myelin sheath” and “Oligodendrocyte development” (FDR-values < 25). Sixteen of the leading edge genes in these gene sets were analysed independently by qPCR, of which 11 genes displayed significant upregulation, including Plp1, Mal, Mag and Cnp (fold change: 1,30, 1,50, 1,30 and 1,15, respectively). Several of the upregulated genes (e.g. MAG, MAL and CNP) have previously been reported as downregulated in post-mortem brain samples from schizophrenia patients. Although caution needs to be taken when extrapolating results from animal studies to humans, the data suggest a role for olanzapine in alleviating myelination-related dysfunction in schizophrenia.

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Olanzapine ameliorates neuropathological changes and increases IGF-1 expression in frontal cortex of C57BL/6 mice exposed to cuprizone

Cited by 22 publications

References 40 publications

Dietary Supplementation With Acer truncatum Oil Promotes Remyelination in a Mouse Model of Multiple Sclerosis

Dietary Supplementation With Acer truncatum Oil Promotes Remyelination in a Mouse Model of Multiple Sclerosis

Microglial activation and progressive brain changes in schizophrenia

Subchronic olanzapine exposure leads to increased expression of myelination-related genes in rat fronto-medial cortex

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