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

TITLE=Tau Knockout and α-Synuclein A53T Synergy Modulated Parvalbumin-Positive Neurons Degeneration Staging in Substantia Nigra Pars Reticulata of Parkinson’s Disease-Liked Model

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.784665

DOI=10.3389/fnagi.2021.784665

ISSN=1663-4365

ABSTRACT=<p>The loss of parvalbumin-positive (PV<sup>+</sup>) 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 <italic>Pitx3-A53T</italic>α<italic>-Syn</italic> × <italic>Tau<sup>–/–</sup></italic> triple transgenic mice model of PD. The aim of this study was to examine the progress of PV<sup>+</sup> neurons loss. We demonstrated that, as compared with non-transgenic (<italic>nTg</italic>) mice, the accumulation of α-<italic>synuclein</italic> in the SNR of aged <italic>Pitx3-A53T</italic>α<italic>-Syn</italic> × <italic>Tau<sup>–/–</sup></italic> mice was increased obviously, which was accompanied by the considerable degeneration of PV<sup>+</sup> neurons and the massive generation of apoptotic NeuN<sup>+</sup>TUNEL<sup>+</sup> co-staining neurons. Interestingly, PV was not costained with TUNEL, a marker of apoptosis. PV<sup>+</sup> 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<sup>+</sup> neurons and the expression of NeuN were rarely observed in the SNR of <italic>nTg</italic> and the other triple transgenic mice. Hence, we propose that <italic>Tau</italic> knockout and α<italic>-syn A53T</italic> synergy modulate PV<sup>+</sup> 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<sup>+</sup> neurons. However, the molecular mechanism needs to be further investigated.</p>