Limits...
Secreted miR-34a in astrocytic shedding vesicles enhanced the vulnerability of dopaminergic neurons to neurotoxins by targeting Bcl-2.

Mao S, Sun Q, Xiao H, Zhang C, Li L - Protein Cell (2015)

Bottom Line: To elucidate the potential role of glial MVs in disease, we evaluated the effects of secreted astrocytic MVs on stress condition.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.These data revealed a novel mechanism underlying astrocyte-neuron interaction in disease.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Nanjing, 210093, China.

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.

No MeSH data available.


Related in: MedlinePlus

SVs derived from LPS-stimulated primary astrocytes accelerates DA neurons loss as well as disease onset in 6-OHDA rat model. (A) Schematic diagram of the experiment process; (B) TH-immunoreactive cell bodies in SN of different groups of rats; (C) Quantification of DA neurons loss among different groups of rats, *P < 0.05 (n = 10 in each group); (D) The Kaplan-Meier curves demonstrate the probability of disease onset, *P < 0.05. (n = 15 in each group)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4491052&req=5

Fig6: SVs derived from LPS-stimulated primary astrocytes accelerates DA neurons loss as well as disease onset in 6-OHDA rat model. (A) Schematic diagram of the experiment process; (B) TH-immunoreactive cell bodies in SN of different groups of rats; (C) Quantification of DA neurons loss among different groups of rats, *P < 0.05 (n = 10 in each group); (D) The Kaplan-Meier curves demonstrate the probability of disease onset, *P < 0.05. (n = 15 in each group)

Mentions: To further understand the role of LPS SVs in vivo, we evaluated the effects of different groups of SVs in the 6-OHDA rat model. We injected 6-OHDA unilaterally into the striatum while simultaneously injecting SVs into the SN in the same side (Fig. 6A). We found that the number of DA neurons was significantly decreased in the LPS SVs-treated rats after 1 week, while blocking the up-regulation of miR-34a in LPS SVs can reduce the DA neuron loss at the same time point. However, when we examined DA neurons 3 weeks after the injection, we found that all groups of rats showed severe DA neuron loss with no significant differences (Figs. 6B and 2C). We further assessed apomorphine-induced contralateral rotation of these rat groups at different time points (1 week, 2 weeks and 3 weeks respectively) after the surgery. Among 15 rats for each group that exhibit abnormal apomorphine-induced rotation at the third week (>6/min), we found that the probability of disease onset of the anti-miR-34a + LPS SV group is 3/15 on the first week and 5/15 on the second week while the numbers in scramble + LPS SV group are 8/15 and 11/15 respectively (Fig. 6D). These results showed that blocking the up-regulation of miR-34a in LPS SVs can significantly delay the disease onset but not able to reverse the disease progression after the injection.Figure 6


Secreted miR-34a in astrocytic shedding vesicles enhanced the vulnerability of dopaminergic neurons to neurotoxins by targeting Bcl-2.

Mao S, Sun Q, Xiao H, Zhang C, Li L - Protein Cell (2015)

SVs derived from LPS-stimulated primary astrocytes accelerates DA neurons loss as well as disease onset in 6-OHDA rat model. (A) Schematic diagram of the experiment process; (B) TH-immunoreactive cell bodies in SN of different groups of rats; (C) Quantification of DA neurons loss among different groups of rats, *P < 0.05 (n = 10 in each group); (D) The Kaplan-Meier curves demonstrate the probability of disease onset, *P < 0.05. (n = 15 in each group)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4491052&req=5

Fig6: SVs derived from LPS-stimulated primary astrocytes accelerates DA neurons loss as well as disease onset in 6-OHDA rat model. (A) Schematic diagram of the experiment process; (B) TH-immunoreactive cell bodies in SN of different groups of rats; (C) Quantification of DA neurons loss among different groups of rats, *P < 0.05 (n = 10 in each group); (D) The Kaplan-Meier curves demonstrate the probability of disease onset, *P < 0.05. (n = 15 in each group)
Mentions: To further understand the role of LPS SVs in vivo, we evaluated the effects of different groups of SVs in the 6-OHDA rat model. We injected 6-OHDA unilaterally into the striatum while simultaneously injecting SVs into the SN in the same side (Fig. 6A). We found that the number of DA neurons was significantly decreased in the LPS SVs-treated rats after 1 week, while blocking the up-regulation of miR-34a in LPS SVs can reduce the DA neuron loss at the same time point. However, when we examined DA neurons 3 weeks after the injection, we found that all groups of rats showed severe DA neuron loss with no significant differences (Figs. 6B and 2C). We further assessed apomorphine-induced contralateral rotation of these rat groups at different time points (1 week, 2 weeks and 3 weeks respectively) after the surgery. Among 15 rats for each group that exhibit abnormal apomorphine-induced rotation at the third week (>6/min), we found that the probability of disease onset of the anti-miR-34a + LPS SV group is 3/15 on the first week and 5/15 on the second week while the numbers in scramble + LPS SV group are 8/15 and 11/15 respectively (Fig. 6D). These results showed that blocking the up-regulation of miR-34a in LPS SVs can significantly delay the disease onset but not able to reverse the disease progression after the injection.Figure 6

Bottom Line: To elucidate the potential role of glial MVs in disease, we evaluated the effects of secreted astrocytic MVs on stress condition.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.These data revealed a novel mechanism underlying astrocyte-neuron interaction in disease.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Nanjing, 210093, China.

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.

No MeSH data available.


Related in: MedlinePlus