Chronic long-term exposure to cuprizone causes severe brain demyelination in mice,which leads to changes in locomotion,working memory and anxiety.These findings suggest the importance of intact myelin for these behaviors.This study aimed to investigate the possible behavioral changes in mice with mild oligodendrocyte/myelin damage that parallels the white matter changes seen in the brains of patients with psychiatric disporders.We used the cuprizonetreated mouse model to test both tissue changes and behavioral functions(locomotor activity,anxiety status,and spatial working memory).The results showed that mice given cuprizone in their diet for 7 days had no significant myelin breakdown as evaluated by immunohistochemical staining for myelin basic protein,while the number of mature oligodendrocytes was reduced.The number and length of Caspr protein clusters,a structural marker of the node of Ranvier,did not change.The locomotor activity of the cuprizonetreated mice increased whereas their anxiety levels were lower than in normal controls;spatial working memory,however,did not change.These results,for the first time,link emotion-related behavior with mild white matter damage in cuprizone-treated mice. 相似文献
Neurological Sciences - To summarize the clinical characteristics of patients with sporadic Creutzfeldt-Jakob disease (sCJD), analyze its sleep disorder characteristics using polysomnography (PSG),... 相似文献
Hemodialysis (HD) is associated with cognitive impairment in patients with end-stage renal disease (ESRD). However, the neural mechanism of spatial working memory (SWM) impairment in HD-ESRD patients remains unclear. We investigated the abnormal alterations in SWM-associated brain activity patterns in HD-ESRD patients using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) technique during n-back tasks. Twenty-two HD-ESRD patients and 22 well-matched controls underwent an fMRI scan while undergoing a three-load n-back tasks with different difficulty levels. Cognitive and mental states were assessed using a battery of neuropsychologic tests. The HD-ESRD patients exhibited worse memory abilities than controls. Compared with the control group, the HD-ESRD patient group showed lower accuracy and longer response time under the n-back tasks, especially in the 2-back task. The patterns of brain activation changed under different working memory loads in the HD-ESRD patients, showing decreased activity in the right medial frontal gyrus and inferior frontal gyrus under 0-back and 1-back task, while more decreased activation in the bilateral frontal cortex, parietal lobule, anterior/posterior cingulate cortex and insula cortex under 2-back task. With the increase of task difficulty, the activation degree of the frontal and parietal cortex decreased. More importantly, we found that lower activation in frontal cortex and parietal lobule was associated with worse cognitive function in the HD-ESRD patients. These results demonstrate that the abnormal brain activity patterns of frontal cortex and parietal lobule may reflect the neural mediation of SWM impairment.
There is growing evidence for the role of smoking in the aetiology of multiple sclerosis (MS). We have undertaken a large case-control study of smoking in MS and assessed this using a regression model. We have confirmed an association between increased risk of MS and smoking in Queensland, Australia, a region of intermediate risk for MS. The overall adjusted odds ratio was 1.9 (95% confidence interval 1.5–2.5) for ever smokers. There was no statistically significant difference in the risks for males and females. A number of potential mechanisms to explain this association have been postulated including direct and indirect (via vitamin D) effects on the immune system. 相似文献
Cuprizone (CPZ) induced demyelinating mouse has been used as an animal model to examine the assumed roles of altered oligodendrocytes in the pathophysiology and treatment of schizophrenia. The objectives of this study were to examine the effect of olanzapine, an atypical antipsychotic, on cuprizone-induced neuropathological changes in the frontal cortex of C57BL/6 mice, and to explore the underlying mechanism for the possible protective effects. The effects of six-week olanzapine (10 mg/kg/day) treatments on neuropathological changes were examined by immunohistochemistry and Western-blot analyses. Olanzapine treatment for six weeks effectively decreased the breakdown of myelin and oligodendrocytes loss of cuprizone-fed mice. Reactive cellular changes, including astrocyte gliosis, microglia accumulation and increased activation of oligodendrocyte progenitor cells, were also attenuated by olanzapine. However, the cortical expression level of insulin-like growth factor 1 (IGF-1) was significantly increased by olanzapine treatment in cuprizone-fed mice as measured by the quantitative real-time polymerase chain reaction (PCR) method. Olanzapine treatment in control mice consuming normal food had no effect on all above measures. These results provide the first in vivo evidence for the protective effects of olanzapine on cuprizone-induced neuropathological changes and suggest that up-regulated insulin-like growth factor 1 may contribute to the protective effects of this antipsychotic. 相似文献