1.Recent advance in role of real-time quaking-induced conversion technique in α-synucleinopathies
Rui ZHANG ; Tingting GAN ; Hengxu MAO ; Xiaokang ZHANG ; Pingyi XU
Chinese Journal of Neuromedicine 2023;22(12):1267-1271
Lewy bodies formed by abnormal deposition of α-synuclein (α-syn) in neurons and glial cells are diagnostic markers of α-synucleinopathies. However, the early diagnosis of α-synucleinopathies is delayed due to the difficulty of brain biopsy at present. Because that α-syn can produce prion-like replication and spread to the periphery under pathological conditions, the ultramicro detection of pathologic α-syn in extracranial tissues by real-time quaking-induced conversion (RT-QuIC) technique can provide a basis for early diagnosis of α-synucleinopathies. In this paper, we review RT-QuIC technique in detecting α-syn seeding activity in different tissues of patients with α-synucleinopathies to summarize the potential value of RT-QuIC technique in early diagnosis or differential diagnosis of α-synucleinopathies.
2.CHCHD2 maintains mitochondrial contact site and cristae organizing system stability and protects against mitochondrial dysfunction in an experimental model of Parkinson’s disease
Lin LU ; Hengxu MAO ; Miaomiao ZHOU ; Yuwan LIN ; Wei DAI ; Jiewen QIU ; Yousheng XIAO ; Mingshu MO ; Xiaoqin ZHU ; Zhuohua WU ; Zhong PEI ; Wenyuan GUO ; Pingyi XU ; Xiang CHEN
Chinese Medical Journal 2022;135(13):1588-1596
Background::Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s dementia. Mitochondrial dysfunction is involved in the pathology of PD. Coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) was identified as associated with autosomal dominant PD. However, the mechanism of CHCHD2 in PD remains unclear.Methods::Short hairpin RNA (ShRNA)-mediated CHCHD2 knockdown or lentivirus-mediated CHCHD2 overexpression was performed to investigate the impact of CHCHD2 on mitochondrial morphology and function in neuronal tumor cell lines represented with human neuroblastoma (SHSY5Y) and HeLa cells. Blue-native polyacrylamide gel electrophoresis (PAGE) and two-dimensional sodium dodecyl sulfate-PAGE analysis were used to illustrate the role of CHCHD2 in mitochondrial contact site and cristae organizing system (MICOS). Co-immunoprecipitation and immunoblotting were used to address the interaction between CHCHD2 and Mic10. Serotype injection of adeno-associated vector-mediated CHCHD2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration were used to examine the influence of CHCHD2 in vivo.Results::We found that the overexpression of CHCHD2 can protect against methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and inhibit the loss of dopaminergic neurons in the MPTP-induced mouse model. Furthermore, we identified that CHCHD2 interacted with Mic10, and overexpression of CHCHD2 can protect against MPP +-induced MICOS impairment, while knockdown of CHCHD2 impaired the stability of MICOS. Conclusion::This study indicated that CHCHD2 could interact with Mic10 and maintain the stability of the MICOS complex, which contributes to protecting mitochondrial function in PD.
3.Displacement characteristics of intraoperative and postoperative positions of electrodes on CT imaging for subthalamic nucleus-deep brain stimulation in Parkinson's disease
Xusheng HOU ; Fengfei LU ; Yongyi YE ; Chen YAO ; Longping YAO ; Yang LU ; Shan XUE ; Xiaozheng HE ; Hengxu MAO ; Xiang SUN ; Baoyan WANG ; Chen QIAN ; Shizhong ZHANG
Chinese Journal of Neuromedicine 2018;17(7):678-684
Objective To investigate the displacement characteristics of intraoperative and postoperative positions of electrodes on CT imaging for bilateral subthalamic nucleus-deep brain stimulation (STN-DBS) in Parkinson's disease (PD).Methods A retrospective analysis on preoperative MR imaging,intraoperative and postoperative CT images of 35 patients with PD treated with STN-DBS in our hospital from January 2014 to June 2018 was performed.A three-dimensional coordinate system was established based on preoperative MR imaging.MR imaging/CT fusion technique was used to fuse intraoperative and postoperative CT images with preoperative MR imaging to locate intraoperative and postoperative electrode positions.The displacement characteristics of intraoperative and postoperative electrodes were analyzed.Results The spatial distance between intraoperative and postoperative positions of bilateral electrodes was about 1 mm,and the depth displacement was minimal.The postoperative position of the first side electrode on lateral axis was shifted outwardly from intraopemtive position,and the second side electrode was shifted internally with a small degree;on anterior-posterior axis,the first side electrode obviously shifted backward,and the second side electrode slightly shifted backward.For bilateral electrodes,corresponding coordinate deviation of three axis between intraoperative electrode-preoperative target and postoperative electrode-preoperative target,showed a significant positive linear correlation,therefore,leading out the coordinate deviation regression function model.Conclusions The displacement of electrodes between intraoperative and postoperative positions has obvious rules after STN-DBS in PD,which can guide the adjustment of intraoperative electrode position and predict the postoperative position of electrode.