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miR-26a and miR-384-5p are required for LTP maintenance and spine enlargement.

Gu QH, Yu D, Hu Z, Liu X, Yang Y, Luo Y, Zhu J, Li Z - Nat Commun (2015)

Bottom Line: Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength.Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities.This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate 'LTP miRNAs'.

View Article: PubMed Central - PubMed

Affiliation: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.

ABSTRACT
Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength. It is associated with the formation and enlargement of dendritic spines-tiny protrusions accommodating excitatory synapses. Both LTP and spine remodelling are crucial for brain development, cognition and the pathophysiology of neurological disorders. The role of microRNAs (miRNAs) in the maintenance of LTP, however, is not well understood. Using next-generation sequencing to profile miRNA transcriptomes, we demonstrate that miR-26a and miR-384-5p specifically affect the maintenance, but not induction, of LTP and different stages of spine enlargement by regulating the expression of RSK3. Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities. This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate 'LTP miRNAs'.

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miR-26a and miR-384-5p are regulated at post-transcriptional levels by GluN2A in LTP.LTP was induced in hippocampal slices by stimulating the Schaffer collateral pathway with high-frequency stimulation. The CA1 region was removed at indicated time points after stimulation for miRNA (a,d), pri-miRNA (b), pre-miRNA (c) and protein analyses (e–h). n=8–9 slices (qRT–PCR) or 4–5 slices (immunoblot) for each condition. Data are presented as mean±s.e.m. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis between unstimulated (a–d) or sham-stimulated (e–h) slices and stimulated slices harvested at different post-stimulation time points. *P<0.05, **P<0.01, ***P<0.001. In a–c, black asterisks indicate statistically significant differences for mature, pri- and pre-miR-26a, and orange asterisks indicate those for mature, pri- and pre-miR-384-5p.
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f7: miR-26a and miR-384-5p are regulated at post-transcriptional levels by GluN2A in LTP.LTP was induced in hippocampal slices by stimulating the Schaffer collateral pathway with high-frequency stimulation. The CA1 region was removed at indicated time points after stimulation for miRNA (a,d), pri-miRNA (b), pre-miRNA (c) and protein analyses (e–h). n=8–9 slices (qRT–PCR) or 4–5 slices (immunoblot) for each condition. Data are presented as mean±s.e.m. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis between unstimulated (a–d) or sham-stimulated (e–h) slices and stimulated slices harvested at different post-stimulation time points. *P<0.05, **P<0.01, ***P<0.001. In a–c, black asterisks indicate statistically significant differences for mature, pri- and pre-miR-26a, and orange asterisks indicate those for mature, pri- and pre-miR-384-5p.

Mentions: To explore how miR-26a and miR-384-5p are regulated in LTP, we first assessed the temporal dynamics and biogenesis of miR-26a and miR-384-5p in LTP. Acute hippocampal slices were stimulated at the Schaffer collateral pathway with four tetanizations for LTP induction. The CA1 region was removed after stimulation for qRT–PCR. Both miR-26a and miR-384-5p exhibited a downward trend, and were significantly reduced by 30 min post stimulation (Fig. 7a). Pri- and pre-miR-26a and -miR-384-5p, by contrast, were not changed significantly by LTP induction (Fig. 7b,c). Conversely, RSK3 protein and phosphorylated rpS6 increased after LTP induction (Fig. 7e–h; Supplementary Fig. 11). These results indicate that the downregulation of miR-26a and miR-384-5p in LTP is post-transcriptional.


miR-26a and miR-384-5p are required for LTP maintenance and spine enlargement.

Gu QH, Yu D, Hu Z, Liu X, Yang Y, Luo Y, Zhu J, Li Z - Nat Commun (2015)

miR-26a and miR-384-5p are regulated at post-transcriptional levels by GluN2A in LTP.LTP was induced in hippocampal slices by stimulating the Schaffer collateral pathway with high-frequency stimulation. The CA1 region was removed at indicated time points after stimulation for miRNA (a,d), pri-miRNA (b), pre-miRNA (c) and protein analyses (e–h). n=8–9 slices (qRT–PCR) or 4–5 slices (immunoblot) for each condition. Data are presented as mean±s.e.m. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis between unstimulated (a–d) or sham-stimulated (e–h) slices and stimulated slices harvested at different post-stimulation time points. *P<0.05, **P<0.01, ***P<0.001. In a–c, black asterisks indicate statistically significant differences for mature, pri- and pre-miR-26a, and orange asterisks indicate those for mature, pri- and pre-miR-384-5p.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403380&req=5

f7: miR-26a and miR-384-5p are regulated at post-transcriptional levels by GluN2A in LTP.LTP was induced in hippocampal slices by stimulating the Schaffer collateral pathway with high-frequency stimulation. The CA1 region was removed at indicated time points after stimulation for miRNA (a,d), pri-miRNA (b), pre-miRNA (c) and protein analyses (e–h). n=8–9 slices (qRT–PCR) or 4–5 slices (immunoblot) for each condition. Data are presented as mean±s.e.m. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis between unstimulated (a–d) or sham-stimulated (e–h) slices and stimulated slices harvested at different post-stimulation time points. *P<0.05, **P<0.01, ***P<0.001. In a–c, black asterisks indicate statistically significant differences for mature, pri- and pre-miR-26a, and orange asterisks indicate those for mature, pri- and pre-miR-384-5p.
Mentions: To explore how miR-26a and miR-384-5p are regulated in LTP, we first assessed the temporal dynamics and biogenesis of miR-26a and miR-384-5p in LTP. Acute hippocampal slices were stimulated at the Schaffer collateral pathway with four tetanizations for LTP induction. The CA1 region was removed after stimulation for qRT–PCR. Both miR-26a and miR-384-5p exhibited a downward trend, and were significantly reduced by 30 min post stimulation (Fig. 7a). Pri- and pre-miR-26a and -miR-384-5p, by contrast, were not changed significantly by LTP induction (Fig. 7b,c). Conversely, RSK3 protein and phosphorylated rpS6 increased after LTP induction (Fig. 7e–h; Supplementary Fig. 11). These results indicate that the downregulation of miR-26a and miR-384-5p in LTP is post-transcriptional.

Bottom Line: Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength.Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities.This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate 'LTP miRNAs'.

View Article: PubMed Central - PubMed

Affiliation: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.

ABSTRACT
Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength. It is associated with the formation and enlargement of dendritic spines-tiny protrusions accommodating excitatory synapses. Both LTP and spine remodelling are crucial for brain development, cognition and the pathophysiology of neurological disorders. The role of microRNAs (miRNAs) in the maintenance of LTP, however, is not well understood. Using next-generation sequencing to profile miRNA transcriptomes, we demonstrate that miR-26a and miR-384-5p specifically affect the maintenance, but not induction, of LTP and different stages of spine enlargement by regulating the expression of RSK3. Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities. This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate 'LTP miRNAs'.

Show MeSH
Related in: MedlinePlus