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Rotenone induced acute miRNA alterations in extracellular vesicles produce mitochondrial dysfunction and cell death

Fatema Currim1,2,3, Josephine Brown-Leung1,3, Tauqeerunnisa Syeda1,3

  • 1School of Health Sciences, Purdue University, West Lafayette, IN, 47907, USA.

NPJ Parkinson'S Disease
|March 28, 2025
PubMed

Insights

Extracellular vesicles (EVs) carrying specific microRNAs (miRNAs) in blood serum can cause Parkinson's disease (PD) pathology. This discovery suggests circulating EVs could serve as early diagnostic markers for PD.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • The role of extracellular vesicles (EVs) in Parkinson's disease (PD) pathogenesis is not fully understood.
  • Investigating EVs' contribution to early PD mechanisms is crucial for developing diagnostic and therapeutic strategies.

Purpose of the Study:

  • To determine if exposure to the PD neurotoxin rotenone alters microRNA (miRNA) profiles in rat EVs.
  • To test if these altered EVs induce PD-relevant neuronal dysfunction and toxicity.

Main Methods:

  • Rats were acutely exposed to the neurotoxin rotenone.
  • MicroRNAs (miRNAs) in cerebrospinal fluid (CSF) and serum-derived EVs were analyzed.
  • Primary midbrain neurons were treated with serum EVs from rotenone-exposed rats.

Main Results:

  • Rotenone exposure induced significant and specific miRNA alterations in serum EVs.
  • EVs from rotenone-treated rats caused oxidative stress, mitochondrial toxicity, and cell death in cultured neurons.
  • These effects were dependent on specific miRNAs, including miR-30a-5p and miR-484.

Conclusions:

  • Differential miRNA expression in circulating EVs may serve as an early diagnostic marker for Parkinson's disease.
  • EV-mediated modulation of cellular functions and viability plays a critical role in PD pathogenesis.

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