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

2022 ◽  
Vol 13 ◽  
Author(s):  
Meige Zheng ◽  
Yanchang Liu ◽  
Zhaoming Xiao ◽  
Luyan Jiao ◽  
Xian Lin

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-A53Tα-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-A53Tα-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.

Brain ◽  
2008 ◽  
Vol 132 (2) ◽  
pp. 309-318 ◽  
Author(s):  
I. A. Prescott ◽  
J. O. Dostrovsky ◽  
E. Moro ◽  
M. Hodaie ◽  
A. M. Lozano ◽  
...  

2022 ◽  
Author(s):  
Min Hyung Seo ◽  
Sujung Yeo

Abstract Parkinson’s disease (PD) is known as the second most common neurodegenerative disease, which is caused by destruction of dopaminergic neurons in the substantia nigra (SN) of the brain; however, the reason for the death of dopaminergic neurons remains unclear. An increase in α-synuclein (α-syn) is considered an important factor in the pathogenesis of PD. In the current study, we investigated the association between PD and serine/arginine-rich protein specific kinase 3 (Srpk3) in MPTP-induced parkinsonism mice model and in SH-SY5Y cells treated with MPP+. Srpk3 expression was significantly downregulated, while tyrosine hydroxylase (TH) decreased and α-synuclein (α-syn) increased after 4 weeks of MPTP intoxication treatment. Dopaminergic cell reduction and α-syn increase were demonstrated by inhibiting Srpk3 expression by siRNA in SH-SY5Y cells. Moreover, a decrease in Srpk3 expression upon siRNA treatment promoted dopaminergic cell reduction and α-syn increase in SH-SY5Y cells treated with MPP+. These results suggest that the decrease in Srpk3 expression due to Srpk3 siRNA caused both a decrease in TH and an increase in α-syn. This raises new possibilities for studying how Srpk3 controls dopaminergic cells and α-syn expression, which may be related to the pathogenesis of PD. Our results provide an avenue for understanding the role of Srpk3 during dopaminergic cell loss and α-syn increase in the SN. Furthermore, this study could support a therapeutic possibility for PD in that the maintenance of Srpk3 expression inhibited dopaminergic cell reduction.


1996 ◽  
Vol 5 (1) ◽  
pp. 49-55 ◽  
Author(s):  
C.D. Hardman ◽  
D.A. McRitchie ◽  
G.M. Halliday ◽  
H.R. Cartwright ◽  
J.G.L. Morris

1998 ◽  
Vol 809 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Yasushi Ishida ◽  
Kazunari Todaka ◽  
Itsumi Kuwahara ◽  
Yuta Ishizuka ◽  
Hiroyuki Hashiguchi ◽  
...  

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