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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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Related in: MedlinePlus

Increased rpS6 phosphorylation caused by the expression change to miR-26a, miR-384-5p and RSK3 in LTP.Primary cortical neurons (DIV4) were transduced with lentivirus-expressing EGFP (as the control), RSK3 siRNA, miR-26a or miR-384-5p. At 2 weeks after transduction, neurons were treated with TEA (25 mM, 15 min) and harvested at 90 min after treatment for immunoblotting. BI-D1870 was added to neural medium at 5 min before TEA treatment. (a) Representative blots. (b) Quantification of a. Data are presented as mean±s.e.m. n=4–5 experiments for each condition. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis. **P<0.01.
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f4: Increased rpS6 phosphorylation caused by the expression change to miR-26a, miR-384-5p and RSK3 in LTP.Primary cortical neurons (DIV4) were transduced with lentivirus-expressing EGFP (as the control), RSK3 siRNA, miR-26a or miR-384-5p. At 2 weeks after transduction, neurons were treated with TEA (25 mM, 15 min) and harvested at 90 min after treatment for immunoblotting. BI-D1870 was added to neural medium at 5 min before TEA treatment. (a) Representative blots. (b) Quantification of a. Data are presented as mean±s.e.m. n=4–5 experiments for each condition. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis. **P<0.01.

Mentions: To further delineate the mechanisms by which miR-26a and miR-384-5p regulate LTP, we examined whether RSK3's substrates are affected by changes in its expression. Primary cortical neurons (DIV17) were treated with TEA (25 mM, 15 min), and lysed at 90 min after treatment for immunoblotting against rpS6, a substrate of the RSK family23. While the total rpS6 level remained unchanged, phosphorylated rpS6 was increased by 2.9±0.3-fold (Fig. 4; Supplementary Fig. 11).


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)

Increased rpS6 phosphorylation caused by the expression change to miR-26a, miR-384-5p and RSK3 in LTP.Primary cortical neurons (DIV4) were transduced with lentivirus-expressing EGFP (as the control), RSK3 siRNA, miR-26a or miR-384-5p. At 2 weeks after transduction, neurons were treated with TEA (25 mM, 15 min) and harvested at 90 min after treatment for immunoblotting. BI-D1870 was added to neural medium at 5 min before TEA treatment. (a) Representative blots. (b) Quantification of a. Data are presented as mean±s.e.m. n=4–5 experiments for each condition. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis. **P<0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Increased rpS6 phosphorylation caused by the expression change to miR-26a, miR-384-5p and RSK3 in LTP.Primary cortical neurons (DIV4) were transduced with lentivirus-expressing EGFP (as the control), RSK3 siRNA, miR-26a or miR-384-5p. At 2 weeks after transduction, neurons were treated with TEA (25 mM, 15 min) and harvested at 90 min after treatment for immunoblotting. BI-D1870 was added to neural medium at 5 min before TEA treatment. (a) Representative blots. (b) Quantification of a. Data are presented as mean±s.e.m. n=4–5 experiments for each condition. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis. **P<0.01.
Mentions: To further delineate the mechanisms by which miR-26a and miR-384-5p regulate LTP, we examined whether RSK3's substrates are affected by changes in its expression. Primary cortical neurons (DIV17) were treated with TEA (25 mM, 15 min), and lysed at 90 min after treatment for immunoblotting against rpS6, a substrate of the RSK family23. While the total rpS6 level remained unchanged, phosphorylated rpS6 was increased by 2.9±0.3-fold (Fig. 4; Supplementary Fig. 11).

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