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自闭症患者背外侧前额叶皮质白质内星形胶质细胞密度无差异的初步证据。

No preliminary evidence of differences in astrocyte density within the white matter of the dorsolateral prefrontal cortex in autism.

机构信息

Department of Psychiatry, The University of Melbourne, Parkville, Australia.

Centre for Neural Engineering, The University of Melbourne, Parkville, Australia.

出版信息

Mol Autism. 2017 Dec 8;8:64. doi: 10.1186/s13229-017-0181-5. eCollection 2017.

Abstract

BACKGROUND

While evidence for white matter and astrocytic abnormalities exist in autism, a detailed investigation of astrocytes has not been conducted. Such an investigation is further warranted by an increasing role for neuroinflammation in autism pathogenesis, with astrocytes being key players in this process. We present the first study of astrocyte density and morphology within the white matter of the dorsolateral prefrontal cortex (DLPFC) in individuals with autism.

METHODS

DLPFC formalin-fixed sections containing white matter from individuals with autism ( = 8, age = 4-51 years) and age-matched controls ( = 7, age = 4-46 years) were immunostained for glial fibrillary acidic protein (GFAP). Density of astrocytes and other glia were estimated via the optical fractionator, astrocyte somal size estimated via the nucleator, and astrocyte process length via the spaceballs probe.

RESULTS

We found no evidence for alteration in astrocyte density within DLPFC white matter of individuals with autism versus controls, together with no differences in astrocyte somal size and process length.

CONCLUSION

Our results suggest that astrocyte abnormalities within the white matter in the DLPFC in autism may be less pronounced than previously thought. However, astrocytic dysregulation may still exist in autism, even in the absence of gross morphological changes. Our lack of evidence for astrocyte abnormalities could have been confounded to an extent by having a small sample size and wide age range, with pathological features potentially restricted to early stages of autism. Nonetheless, future investigations would benefit from assessing functional markers of astrocytes in light of the underlying pathophysiology of autism.

摘要

背景

自闭症存在白质和星形胶质细胞异常的证据,但尚未对星形胶质细胞进行详细研究。神经炎症在自闭症发病机制中的作用越来越大,星形胶质细胞是该过程的关键参与者,这进一步证明了进行这种研究的必要性。我们首次研究了自闭症个体背外侧前额叶皮质(DLPFC)白质内的星形胶质细胞密度和形态。

方法

对来自自闭症个体(n=8,年龄 4-51 岁)和年龄匹配对照者(n=7,年龄 4-46 岁)的福尔马林固定的 DLPFC 切片进行胶质纤维酸性蛋白(GFAP)免疫染色。通过光学分割器估计星形胶质细胞和其他胶质细胞的密度,通过核器估计星形胶质细胞体大小,通过空间球探针估计星形胶质细胞突起长度。

结果

我们未发现自闭症个体与对照者相比,DLPFC 白质内星形胶质细胞密度存在改变,星形胶质细胞体大小和突起长度也无差异。

结论

我们的结果表明,自闭症患者 DLPFC 白质内的星形胶质细胞异常可能不如先前认为的那么明显。然而,即使没有明显的形态学变化,自闭症中仍可能存在星形胶质细胞功能失调。由于样本量小且年龄范围广,我们缺乏星形胶质细胞异常的证据,这可能在一定程度上受到了限制,而且病理性特征可能仅限于自闭症的早期阶段。尽管如此,未来的研究仍需要根据自闭症的潜在病理生理学,评估星形胶质细胞的功能标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4299/5721546/af3e420dd8e6/13229_2017_181_Fig1_HTML.jpg

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