Dataset Information

MiR-101a-3p Impairs Synaptic Plasticity and Contributes to Synucleinopathy.

ABSTRACT:

Background

Synucleinopathies are disorders characterized by the abnormal accumulation of α-synuclein (aSyn). Synaptic compromise is observed in synucleinopathies parallel to aSyn aggregation and is accompanied by transcript deregulation.

Objective

We sought to identify microRNAs associated with synaptic processes that may contribute to synaptic dysfunction and degeneration in synucleinopathies.

Methods

We performed small RNA-sequencing of midbrain from 6-month-old transgenic mice expressing A30P mutant aSyn, followed by comparative expression analysis. We then used real-time quantitative polymerase chain reaction (qPCR) for validation. Functional analysis was performed in primary neurons by biochemical assays and imaging.

Results

We found several deregulated biological processes linked to the synapse. miR-101a-3p was validated as a synaptic miRNA upregulated in aSyn Tg mice and in the cortex of dementia with Lewy bodies patients. Mice and primary cultured neurons overexpressing miR-101a-3p showed downregulation of postsynaptic proteins GABA Ab2 and SAPAP3 and altered dendritic morphology resembling synaptic plasticity impairments and/or synaptic damage. Interestingly, primary cultured neuron exposure to recombinant wild-type aSyn species efficiently increased miR-101a-3p levels. Finally, a dynamic role of miR-101a-3p in synapse plasticity was shown by identifying downregulation of miR-101a-3p in a condition of enhanced synaptic plasticity modelled in Wt animals housed in enriched environment.

Conclusion

To conclude, we correlated pathologic aSyn with high levels of miR-101a-3p and a novel dynamic role of the miRNA in synaptic plasticity.

SUBMITTER: Xylaki M

PROVIDER: S-EPMC10041420 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

miR-101a-3p Impairs Synaptic Plasticity and Contributes to Synucleinopathy.

Xylaki Mary M Paiva Isabel I Al-Azzani Mohammed M Gerhardt Ellen E Jain Gaurav G Islam Md Rezaul MR Vasili Eftychia E Wassouf Zinah Z Schulze-Hentrich Julia M JM Fischer André A Outeiro Tiago Fleming TF

Journal of Parkinson's disease 20230101 2

<h4>Background</h4>Synucleinopathies are disorders characterized by the abnormal accumulation of α-synuclein (aSyn). Synaptic compromise is observed in synucleinopathies parallel to aSyn aggregation and is accompanied by transcript deregulation.<h4>Objective</h4>We sought to identify microRNAs associated with synaptic processes that may contribute to synaptic dysfunction and degeneration in synucleinopathies.<h4>Methods</h4>We performed small RNA-sequencing of midbrain from 6-month-old transgeni ...[more]

PMID: 36744345

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