The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence
Por:
S. MELLADO, M. MORILLO-BARGUES, C. PERPIÑÁ-CLÉRIGUES, F. GARCÍA-GARCÍA, V. MORENO-MANZANO, C. GUERRI and M. PASCUAL
Publicada:
1 abr 2025
Resumen:
Our previous studies have reported that activation of the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been shown to restore the neuroinflammatory response, along with myelin and synaptic structural alterations in the prefrontal cortex, and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice. Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles, the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue, which inhibited the activation of the NLRP3 inflammasome, was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking. We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes (e.g., pyrin domain-containing 1, caspase recruitment domain-containing 4, and absent in melanoma 2, as well as the alterations in inflammatory genes (interleukin-1 beta, interleukin-18, inducible nitric oxide synthase, nuclear factor-kappa B, monocyte chemoattractant protein-1, and C-X3-C motif chemokine ligand 1) and miRNAs (miR-21a-5p, miR-146a-5p, and miR-141-5p) induced by binge-like ethanol treatment in adolescent mice. Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways. Taken together, these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.
Filiaciones:
S. MELLADO:
Univ Valencia, Sch Med & Dent, Dept Physiol, Valencia, Spain
M. MORILLO-BARGUES:
Univ Valencia, Sch Med & Dent, Dept Physiol, Valencia, Spain
C. PERPIÑÁ-CLÉRIGUES:
Univ Valencia, Sch Med & Dent, Dept Physiol, Valencia, Spain
Principe Felipe Res Ctr, Bioinformat & Biostat Unit, Valencia, Spain
:
Principe Felipe Res Ctr, Bioinformat & Biostat Unit, Valencia, Spain
V. MORENO-MANZANO:
Principe Felipe Res Ctr, Neuronal & Tissue Regenerat Lab, Valencia, Spain
C. GUERRI:
Univ Valencia, Sch Med & Dent, Dept Physiol, Valencia, Spain
:
Univ Valencia, Sch Med & Dent, Dept Physiol, Valencia, Spain
gold, Green Submitted
|