Leggio 2022 Adv Healthc Mater
| Leggio L, L'Episcopo F, Magrì A, Ulloa-Navas MJ, Paternò G, Vivarelli S, Bastos CAP, Tirolo C, Testa N, Caniglia S, Risiglione P, Pappalardo F, Serra A, García-Tárraga P, Faria N, Powell JJ, Peruzzotti-Jametti L, Pluchino S, García-Verdugo JM, Messina A, Marchetti B, Iraci N (2022) Small extracellular vesicles secreted by nigrostriatal astrocytes rescue cell death and preserve mitochondrial function in Parkinson's disease. https://doi.org/10.1002/adhm.202201203 |
» Adv Healthc Mater 11:e2201203. PMID: 35856921 Open Access
Leggio Loredana, L'Episcopo Francesca, Magri Andrea, Ulloa-Navas Maria Jose, Paterno Greta, Vivarelli Silvia, Bastos Carlos AP, Tirolo Cataldo, Testa Nunzio, Caniglia Salvatore, Risiglione Pierpaolo, Pappalardo Fabrizio, Serra Alessandro, Garcia-Tarraga Patricia, Faria Nuno, Powell Jonathan J, Peruzzotti-Jametti Luca, Pluchino Stefano, Garcia-Verdugo Jose Manuel, Messina Angela, Marchetti Bianca, Iraci Nunzio (2022) Adv Healthc Mater
Abstract: Extracellular vesicles (EVs) are emerging as powerful players in cell-to-cell communication both in healthy and diseased brain. In Parkinson's disease (PD)-characterized by selective dopaminergic neuron death in ventral midbrain (VMB) and degeneration of their terminals in striatum (STR)-astrocytes exert dual harmful/protective functions, with mechanisms not fully elucidated. Here, this study shows that astrocytes from the VMB-, STR-, and VMB/STR-depleted brains release a population of small EVs in a region-specific manner. Interestingly, VMB-astrocytes secreted the highest rate of EVs, which is further exclusively increased in response to CCL3, a chemokine that promotes robust dopaminergic neuroprotection in different PD models. The neuroprotective potential of nigrostriatal astrocyte-EVs is investigated in differentiated versus undifferentiated SH-SY5Y cells exposed to oxidative stress and mitochondrial toxicity. EVs from both VMB- and STR-astrocytes counteract H2O2 -induced caspase-3 activation specifically in differentiated cells, with EVs from CCL3-treated astrocytes showing a higher protective effect. High resolution respirometry further reveals that nigrostriatal astrocyte-EVs rescue neuronal mitochondrial complex I function impaired by the neurotoxin MPP+. Notably, only EVs from VMB-astrocyte fully restore ATP production, again specifically in differentiated SH-SY5Y. These results highlight a regional diversity in the nigrostriatal system for the secretion and activities of astrocyte-EVs, with neuroprotective implications for PD. • Keywords: Parkinson's disease, Astrocytes, Exosomes, Extracellular vesicles, High-resolution respirometry, Mitochondria • Bioblast editor: Plangger M • O2k-Network Lab: IT Catania Messina A
Labels: MiParea: Respiration
Pathology: Parkinson's
Organism: Human Tissue;cell: Neuroblastoma Preparation: Permeabilized cells, Intact cells
Coupling state: LEAK, ROUTINE, OXPHOS, ET
Pathway: N, S, NS, ROX
HRR: Oxygraph-2k
2022-08
