LncRNA BDNF-AS promotes autophagy and apoptosis in MPTP-induced Parkinson's disease via ablating microRNA-125b-5p

Yan Fan; Xue Zhao; Kai Lu; Guizhi Cheng

doi:10.1016/j.brainresbull.2020.02.003

LncRNA BDNF-AS promotes autophagy and apoptosis in MPTP-induced Parkinson's disease via ablating microRNA-125b-5p

Brain Res Bull. 2020 Apr:157:119-127. doi: 10.1016/j.brainresbull.2020.02.003. Epub 2020 Feb 10.

Authors

Yan Fan¹, Xue Zhao¹, Kai Lu², Guizhi Cheng³

Affiliations

¹ Department of Neurology, Liaocheng People's Hospital, No. 67, West Dongchang Road, Liaocheng City, Shandong Province, 252000, China.
² Department of Neurology, Liaocheng Third People's Hospital, No. 62, Weiyu Road, Liaocheng City, Shandong Province, 252000, China.
³ Department of Neurology, Liaocheng Guangming Hospital, No. 87, North Changrun Road, Liaocheng City, Shandong Province, 252000, China. Electronic address: chengguizhi25@163.com.

PMID: 32057951
DOI: 10.1016/j.brainresbull.2020.02.003

Abstract

Backgrounds: Recently, extensive evidence has indicated that the biological role of long non-coding RNAs (lncRNAs) in neurodegenerative diseases is becoming increasingly evident. The lncRNA brain-derived neurotrophic factor anti-sense (BDNF-AS) has been found to be dysregulated in Huntington's Disease. However, the function of BDNF-AS in Parkinson's disease (PD) remains unknown. The purpose of this present study was to explore the effect of BDNF-AS on PD and its underlying molecular mechanisms.

Methods: The MPTP-induced mouse model of PD and MPP+-induced SH-SY5Y cell model were established. Immunofluorescence was performed to determine the number of TH + positive cells. Mice behavioral changes were detected by pole and rota-rod test. SH-SY5Y cells viability, apoptosis was detected by MTT assay and flow cytometry. The number of autophagosome was measured by transmission electron microscopy. Dopamine content was tested by high performance liquid chromatography. Dual-luciferase reporter gene assay was utilized to verify the correlation between BDNF-AS and miR-125b-5p. qRT-PCR and western blot were used to detect gene expression levels.

Results: Our results showed that BDNF-AS was up-regulated in MPTP-induced PD model and dopamine neurons, and MPP + treated SH-SY5Y cells, while miR-125b-5p was down-regulated. The expression of BDNF-AS was positively related with the MPP + concentration. BDNF-AS knockdown could significantly promote cell proliferation, while inhibit apoptosis and autophagy in SH-SY5Y cells treated by MPP + . Silencing BDNF-AS could also increase TH positive neurons and significantly suppress the autophagy of PD mice. Additionally, miR-125b-5p, a putative target gene of BDNF-AS, was involved in the effects of BDNF-AS on SH-SY5Y cell apoptosis and autophagy.

Conclusions: Our study demonstrated that knockdown of BDNF-AS could elevate SH-SY5Y cell viability, inhibit autophagy and apoptosis in MPTP-induced PD models through regulating miR-125b-5p, suggesting that BDNF-AS might act as a potential therapeutic target for PD.

Keywords: Apoptosis; Autophagy; BDNF-AS; Parkinson’s disease; miR-125b-5p.

MeSH terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
Animals
Autophagy / physiology*
Brain-Derived Neurotrophic Factor / metabolism*
Cell Line, Tumor
Cell Proliferation / physiology*
Cell Survival / physiology
Mice, Inbred C57BL
Neurons / metabolism*
Parkinson Disease / genetics
Parkinson Disease / metabolism*
RNA, Long Noncoding / metabolism

Substances

Brain-Derived Neurotrophic Factor
RNA, Long Noncoding
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine