期刊
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
卷 71, 期 2, 页码 148-161出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/NEN.0b013e318244477d
关键词
Cerebellar ataxia; Mitochondrial DNA; Mitochondrial disease; Neurodegeneration; Olivo-cerebellum
资金
- Wellcome Trust [074454/Z/04/Z]
- Newcastle University Centre for Brain Ageing
- BBSRC
- EPSRC
- ESRC
- MRC
- cross-council Lifelong Health and Wellbeing Initiative [G0700718]
- UK NIHR Biomedical Research Centre
- Newcastle upon Tyne Hospitals NHS Foundation Trust
- UK NHS Specialist Commissioners
- UK Medical Research Council [G0400074]
- Alzheimer's Society and Alzheimer's Research Trust
- MRC [G0400074, G0502157, G0800674, G0900652, G0700718, MC_G0802536, G1100540] Funding Source: UKRI
- Medical Research Council [G0700718B, G0700718, G1100540, MC_G0802536, G0900652, G0502157, G0400074, G0800674] Funding Source: researchfish
Cerebellar ataxia is a prominent clinical symptom in patients with mitochondrial DNA (mtDNA) disease. This is often progressive with onset in young adulthood. We performed a detailed neuropathologic investigation of the olivary-cerebellum in 14 genetically and clinically well-defined patients with mtDNA disease. Quantitative neuropathologic investigation showed varying levels of loss of Purkinje cells and neurons of the dentate nucleus and inferior olivary nuclei. Typically, focal Purkinje cell loss was present in patients with the m. 3243A>G mutation caused by the presence of microinfarcts, with relative preservation of neuronal cell populations in the olivary and dentate nuclei. In contrast, patients with the m. 8344A>G mutation or recessive POLG mutations showed extensive and global neuronal cell loss in all 3 olivary-cerebellum areas examined. Molecular analysis of mutated mtDNA heteroplasmy levels revealed that neuronal cell loss occurred independently of the level of mutated mtDNA present within surviving neurons. High levels of neuronal respiratory chain deficiency, particularly of complex I, were detected in surviving cells;
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据