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Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
Published on: August 15, 2017
Expression profiling of synaptic microRNAs from the adult rat brain identifies regional differences and
Israel Pichardo-Casas1, Loyal A Goff, Mavis R Swerdel
1Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, DF México. pichardo@email.ifc.unam.mx
Abstract:
In recent years, microRNAs or miRNAs have been proposed to target neuronal mRNAs localized near the synapse, exerting a pivotal role in modulating local protein synthesis, and presumably affecting adaptive mechanisms such as synaptic plasticity. In the present study we have characterized the distribution of miRNAs in five regions of the adult mammalian brain and compared the relative abundance between total fractions and purified synaptoneurosomes (SN), using three different methodologies. The results show selective enrichment or depletion of some miRNAs when comparing total versus SN fractions. These miRNAs were different for each brain region explored. Changes in distribution could not be attributed to simple diffusion or to a targeting sequence inside the miRNAs. In silico analysis suggest that the differences in distribution may be related to the preferential concentration of synaptically localized mRNA targeted by the miRNAs. These results favor a model of co-transport of the miRNA-mRNA complex to the synapse, although further studies are required to validate this hypothesis. Using an in vivo model for increasing excitatory activity in the cortex and the hippocampus indicates that the distribution of some miRNAs can be modulated by enhanced neuronal (epileptogenic) activity. All these results demonstrate the dynamic modulation in the local distribution of miRNAs from the adult brain, which may play key roles in controlling localized protein synthesis at the synapse.
Insights
MicroRNAs (miRNAs) show varied distribution in adult brain regions, with some concentrating at synapses. This dynamic localization, potentially involving co-transport with mRNA, may regulate synaptic plasticity and protein synthesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are implicated in regulating gene expression, particularly in neuronal function.
- Their role in local protein synthesis at synapses and synaptic plasticity is an emerging area of research.
Purpose of the Study:
- To investigate the distribution and relative abundance of miRNAs in different adult mammalian brain regions.
- To compare miRNA profiles between total brain fractions and purified synaptoneurosomes (SN).
- To explore the mechanisms and activity-dependent modulation of miRNA localization.
Main Methods:
- Characterization of miRNA distribution across five adult mammalian brain regions.
- Comparison of miRNA abundance in total brain fractions versus purified synaptoneurosomes (SN) using three distinct methodologies.
- In silico analysis to predict miRNA-mRNA interactions and localization mechanisms.
- In vivo studies using an epilepsy model to assess activity-dependent miRNA modulation.
Main Results:
- Selective enrichment or depletion of specific miRNAs was observed in SN fractions compared to total brain fractions, varying by brain region.
- MiRNA distribution changes were not explained by simple diffusion or miRNA targeting sequences.
- In silico analysis suggested miRNA localization is linked to the synaptic concentration of their targeted mRNAs.
- Enhanced neuronal activity (epileptogenic) modulated the distribution of certain miRNAs in vivo.
Conclusions:
- MiRNAs exhibit dynamic, region-specific localization within the adult brain, with a subset preferentially accumulating at synapses.
- Evidence supports a model of miRNA-mRNA complex co-transport to synaptic sites.
- Neuronal activity can dynamically alter miRNA distribution, suggesting a role in adaptive synaptic mechanisms.
- These findings highlight the importance of localized miRNA regulation in synaptic function and plasticity.

