Highlights
- •Rho and ROCK knockout may reduce the damage by MPTP on mice behavior.
- •Rho and ROCK knockout protects dopaminergic neuron from injury.
- •Rho and ROCK knockout decreases Rho, ROCK, Sema3A and relevant factor mRNA expression.
- •Rho and ROCK knockout reduces Rho, ROCK, Sema3A and relevant factor proteins.
- •Rho and ROCK gene can serve as novel therapeutic targets of PD.
Abstract
Objective
The present study aims to elucidate the role of Rho-mediated ROCK-Semaphorin3A signaling
pathway in the pathogenesis of Parkinson's disease (PD) in a mouse model.
Methods
One-hundred twelve eight-week male C57BL/6 mice were selected. The mouse model of
PD was constructed by intraperitoneal injection of MPTP. All mice were divided into
four groups (28 mice in each group): Blank group, Model group, Rho knockout (Rho+/−) group and ROCK knockout (ROCK+/−) group. Changes of behavior of the mice were studied through automatic moving
test and rotarod test. Immunohistochemistry (IHC) was used to detect the expressions
of TH, CD11b and GFAP. High performance liquid chromatograph (HPLC) was performed
for detection of dopamine and its metabolic product. The mRNA and protein expressions
of Rho, ROCK, Sema3A, PlexinA and NRP-1 were detected using quantitative real-time
polymerase chain reaction (qRT-PCR) and Western blotting.
Results
Rho and ROCK knockout improved the damage caused by MPTP on the behavior of mice and
protected dopaminergic neurons from injury, along with the increases of dopamine and
its metabolic product. The mRNA and protein expressions of Rho, ROCK, Sema3A, PlexinA
and NRP-1 were increased in PD mice in the Model group compared with those in the
Blank group. Compared to the Model group, the mRNA and protein expressions of Rho,
ROCK, Sema3A, PlexinA and NRP-1 were reduced in the Rho+/− and ROCK+/− groups.
Conclusion
These findings indicate that Rho and ROCK knockout may improve the behavior of mice
and prevent MPTP-induced dopaminergic neurons damage by regulating Sema3A, PlexinA
and NRP-1 in a mouse model of PD.
Keywords
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Article info
Publication history
Published online: August 30, 2016
Accepted:
August 29,
2016
Received in revised form:
August 5,
2016
Received:
May 28,
2016
Identification
Copyright
© 2016 Elsevier B.V. All rights reserved.
