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帕金森病样模型黑质网状部中敲除及α-协同调节的小白蛋白阳性神经元变性分期

Knockout and α- Synergy Modulated Parvalbumin-Positive Neurons Degeneration Staging in Substantia Nigra Pars Reticulata of Parkinson's Disease-Liked Model.

作者信息

Zheng Meige, Liu Yanchang, Xiao Zhaoming, Jiao Luyan, Lin Xian

机构信息

Department of Orthopaedics, The Second Hospital of Anhui Medical University, Hefei, China.

Nuwacell Biotechnologies Co., Ltd, Hefei, China.

出版信息

Front Aging Neurosci. 2022 Jan 11;13:784665. doi: 10.3389/fnagi.2021.784665. eCollection 2021.

Abstract

The loss of parvalbumin-positive (PV) neurons in the substantia nigra pars reticulata (SNR) was observed in patients with end-stage Parkinson's disease (PD) and our previously constructed old-aged α × triple transgenic mice model of PD. The aim of this study was to examine the progress of PV neurons loss. We demonstrated that, as compared with non-transgenic () mice, the accumulation of α- in the SNR of aged α × mice was increased obviously, which was accompanied by the considerable degeneration of PV neurons and the massive generation of apoptotic NeuNTUNEL co-staining neurons. Interestingly, PV was not costained with TUNEL, a marker of apoptosis. PV neurons in the SNR may undergo a transitional stage from decreased expression of PV to increased expression of NeuN and then to TUNEL expression. In addition, the degeneration of PV neurons and the expression of NeuN were rarely observed in the SNR of and the other triple transgenic mice. Hence, we propose that knockout and α synergy modulate PV neurons degeneration staging in the SNR of aged PD-liked mice model, and NeuN may be suited for an indicator that suggests degeneration of SNR PV neurons. However, the molecular mechanism needs to be further investigated.

摘要

在晚期帕金森病(PD)患者以及我们先前构建的老年α-synuclein三倍转基因PD小鼠模型中,观察到黑质网状部(SNR)中小清蛋白阳性(PV)神经元的丢失。本研究的目的是检测PV神经元丢失的进程。我们证明,与非转基因()小鼠相比,老年α-synuclein小鼠SNR中α-synuclein的积累明显增加,同时伴有PV神经元的显著退化和大量凋亡的NeuN/TUNEL共染色神经元的产生。有趣的是,PV未与凋亡标志物TUNEL共染色。SNR中的PV神经元可能经历一个从PV表达降低到NeuN表达增加再到TUNEL表达的过渡阶段。此外,在和其他三倍转基因小鼠的SNR中很少观察到PV神经元的退化和NeuN的表达。因此,我们提出敲除和α-synuclein协同作用调节老年PD样小鼠模型SNR中PV神经元的退化分期,并且NeuN可能适合作为提示SNR中PV神经元退化的指标。然而,其分子机制仍需进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/8787263/70e56fea058b/fnagi-13-784665-g001.jpg

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