Abstract
MicroRNAs (miRNAs) are a class of noncoding RNAs that regulates target gene expression at posttranscriptional level, leading to further biological functions. We have demonstrated that microvesicles (MVs) can deliver miRNAs into target cells as a novel way of intercellular communication. It is reported that in central nervous system, glial cells release MVs, which modulate neuronal function in normal condition. To elucidate the potential role of glial MVs in disease, we evaluated the effects of secreted astrocytic MVs on stress condition. Our results demonstrated that after Lipopolysaccharide (LPS) stimulation, astrocytes released shedding vesicles (SVs) that enhanced vulnerability of dopaminergic neurons to neurotoxin. Further investigation showed that increased astrocytic miR-34a in SVs was involved in this progress via targeting anti-apoptotic protein Bcl-2 in dopaminergic neurons. We also found that inhibition of astrocytic miR-34a after LPS stimulation can postpone dopaminergic neuron loss under neurotoxin stress. These data revealed a novel mechanism underlying astrocyte-neuron interaction in disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-015-0168-y) contains supplementary material, which is available to authorized users.
Highlights
Parkinson’s disease (PD) is characterized by the progressive degeneration of dopamine (DA) neurons in the substantia nigra (SN)
Because it has been reported that miR-34a targets Bcl-2 protein, which regulates cell apoptosis, we proposed that up-regulation of miR-34a in LPS shedding vesicles (SVs) may contribute to the increased vulnerability of SHSY5Y cells to neurotoxins via repressing Bcl-2 expression
We revealed a novel mechanism by which astrocytes can influence neuronal survival under PD conditions
Summary
Parkinson’s disease (PD) is characterized by the progressive degeneration of dopamine (DA) neurons in the substantia nigra (SN). Further investigation produced evidence that MVs released from microglia stimulate synaptic activity via enhanced sphingolipid metabolism, indicating that microglia MVs may have significant biological functions under normal conditions (Antonucci et al, 2012). In recent years, accumulating evidence showed that secreted miRNAs in MVs have significant biological functions including effects on cell proliferation, development, differentiation as well as cell death and cancer progression (Hu et al, 2012; Janowska-Wieczorek et al, 2005; Jung and Suh, 2014; Liu et al, 2013; Vlassov et al, 2012; Zhou et al, 2014; Zhu and Fan, 2011). There are few studies regarding the function of secreted miRNAs in neuron-glia interaction of the central nervous system either in physiological or disease conditions. Whether secreted miRNAs in astrocytic MVs are involved in PD pathogenesis is still unknown; it is important to investigate the potential role of MVs in astrocyteneuron interactions in PD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
