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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  Pitx3-A53T α -Syn  ×  Tau –/–   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 ( nTg ) mice, the accumulation of α- synuclein  in the SNR of aged  Pitx3-A53T α -Syn  ×  Tau –/–   mice was increased obviously, which was accompanied by the considerable degeneration of PV +  neurons and the massive generation of apoptotic NeuN + TUNEL +  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  nTg  and the other triple transgenic mice. Hence, we propose that  Tau  knockout and α -syn A53T  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.

frontiers in aging neuroscience

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