OBJECTIVE: Parkinson's disease (PD) is a frequent degenerative disease of the nervous system with undefined pathogenesis. This study explored the protective effect of microRNA (miR)-218-5p on dopaminergic neuron injury in substantia nigra (SN) of rats with PD through the regulation of LIM and SH3 domain protein 1 (LASP1). METHODS: The PD rat model was established by fixed point injection of 6-hydroxydopamine into the rats. The PD rats were injected with miR-218-5p overexpressed recombinant adeno-associated virus (rAAV) or LASP1 silenced rAAV to explore their roles in dopaminergic neurons in SN of rats with PD. The changes in pathological structure of SN were observed and the expression of tyrosine hydroxylase (TH) and deacetylvindoline acetyltransferase (DAT), the dopaminergic neuron apoptosis and oxidative stress factor in the SN were detected. The expression of miR-218-5p, LASP1, Bcl-2 and Bax in SN was detected. The targeting relationship between miR-218-5p and LASP1 was confirmed. RESULTS: Declined miR-218-5p and overexpressed LASP1 existed in the brain SN of PD rats. Up-regulated miR-218-5p or inhibited LASP1 improved the pathological damage of dopaminergic neurons and increased the number of TH and DAT positive cells in brain SN of PD rats. Furthermore, elevated miR-218-5p or depressed LASP1 inhibited the apoptosis, and oxidative stress of dopaminergic neurons in brain SN of PD rats. In addition, increased miR-218-5p repressed the expression of LASP1 in the brain SN of PD rats. LASP1 was proven to be a direct target of miR-218-5p. CONCLUSION: The study highlights that up-regulated miR-218-5p could improve the damage of dopaminergic neurons in PD rats, which was related to the inhibition of LASP1.
OBJECTIVE: Parkinson's disease (PD) is a frequent degenerative disease of the nervous system with undefined pathogenesis. This study explored the protective effect of microRNA (miR)-218-5p on dopaminergic neuron injury in substantia nigra (SN) of rats with PD through the regulation of LIM and SH3 domain protein 1 (LASP1). METHODS: The PD rat model was established by fixed point injection of 6-hydroxydopamine into the rats. The PD rats were injected with miR-218-5p overexpressed recombinant adeno-associated virus (rAAV) or LASP1 silenced rAAV to explore their roles in dopaminergic neurons in SN of rats with PD. The changes in pathological structure of SN were observed and the expression of tyrosine hydroxylase (TH) and deacetylvindoline acetyltransferase (DAT), the dopaminergic neuron apoptosis and oxidative stress factor in the SN were detected. The expression of miR-218-5p, LASP1, Bcl-2 and Bax in SN was detected. The targeting relationship between miR-218-5p and LASP1 was confirmed. RESULTS: Declined miR-218-5p and overexpressed LASP1 existed in the brain SN of PD rats. Up-regulated miR-218-5p or inhibited LASP1 improved the pathological damage of dopaminergic neurons and increased the number of TH and DAT positive cells in brain SN of PD rats. Furthermore, elevated miR-218-5p or depressed LASP1 inhibited the apoptosis, and oxidative stress of dopaminergic neurons in brain SN of PD rats. In addition, increased miR-218-5p repressed the expression of LASP1 in the brain SN of PD rats. LASP1 was proven to be a direct target of miR-218-5p. CONCLUSION: The study highlights that up-regulated miR-218-5p could improve the damage of dopaminergic neurons in PD rats, which was related to the inhibition of LASP1.
Authors: Mohamed Ashmwe; Katja Posa; Alexander Rührnößl; Johannes Christoph Heinzel; Patrick Heimel; Michael Mock; Barbara Schädl; Claudia Keibl; Sebastien Couillard-Despres; Heinz Redl; Rainer Mittermayr; David Hercher Journal: Biomedicines Date: 2022-07-07