Increased occurrence of pathological mitochondria in astrocytic perivascular endfoot processes and neurons of idiopathic intracranial hypertension,Journal of Neuroscience Research

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Increased occurrence of pathological mitochondria in astrocytic perivascular endfoot processes and neurons of idiopathic intracranial hypertension
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2020-10-26 , DOI: 10.1002/jnr.24743
Per Kristian Eide _{1,

2} , Md Mahdi Hasan-Olive _{1,

2} , Hans-Arne Hansson ₃ , Rune Enger _{4,

5}

Affiliation

Idiopathic intracranial hypertension (IIH) primarily affects fertile, overweight women, and presents with the symptoms of raised intracranial pressure. The etiology is unknown but has been thought to relate to cerebrospinal fluid disturbance or cerebral venous stenosis. We have previously found evidence that IIH is also a disease of the brain parenchyma, evidenced by alterations at the neurogliovascular interface, including astrogliosis, pathological changes in the basement membrane and pericytes, and alterations of perivascular aquaporin‐4. The aim of this present electron microscopic study was to examine whether mitochondria phenotype was changed in IIH, particularly focusing on perivascular astrocytic endfeet and neurons (soma and pre‐ and postsynaptic terminals). Cortical brain biopsies of nine reference individuals and eight IIH patients were analyzed for subcellular distribution and phenotypical features of mitochondria using transmission electron microscopy. We found significantly increased prevalence of pathological mitochondria and reduced number of normal mitochondria in astrocytic endfeet of IIH patients. The degree of astrogliosis correlated negatively with the number of normal mitochondria in astrocytic endfoot processes. Moreover, we found significantly increased number of pathological mitochondria in pre‐ and postsynaptic neuronal terminals, as well as significantly shortened distance between mitochondria and endoplasmic reticulum contacts. Finally, the length of postsynaptic density, a marker of synaptic strength, was on average reduced in IIH. The present data provide evidence of pathological mitochondria in perivascular astrocytes endfeet and neurons of IIH patients, highlighting that impaired metabolism at the neurogliovascular interface may be a facet of IIH.

中文翻译：

星形细胞血管周围终足突和特发性颅内高压神经元中病理性线粒体的发生率增加

特发性颅内高压（IIH）主要影响生育能力超重的女性，并表现为颅内压升高的症状。病因尚不清楚，但被认为与脑脊液紊乱或脑静脉狭窄有关。我们之前发现的证据表明 IIH 也是一种脑实质疾病，表现为神经胶质血管界面的改变，包括星形胶质细胞增生、基底膜和周细胞的病理变化以及血管周围水通道蛋白-4 的改变。本电子显微镜研究的目的是检查 IIH 中线粒体表型是否发生变化，特别关注血管周围星形胶质细胞末足和神经元（胞体以及突触前和突触后末端）。使用透射电子显微镜分析了 9 名参考个体和 8 名 IIH 患者的皮质脑活检，以了解线粒体的亚细胞分布和表型特征。我们发现 IIH 患者星形胶质细胞终足中病理性线粒体的患病率显着增加，正常线粒体数量减少。星形胶质细胞增生的程度与星形细胞终足突中正常线粒体的数量呈负相关。此外，我们发现突触前和突触后神经元末梢的病理线粒体数量显着增加，并且线粒体和内质网接触之间的距离显着缩短。最后，突触后密度的长度（突触强度的标志）在 IIH 中平均减少。目前的数据提供了 IIH 患者血管周围星形胶质细胞末足和神经元中病理性线粒体的证据，强调神经胶质血管界面代谢受损可能是 IIH 的一个方面。

更新日期：2020-12-20

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