Transfer of pathological α-synuclein from neurons to astrocytes via exosomes causes inflammatory responses after METH exposure
| Autor: | Yitong He, Pingming Qiu, Jiuyang Ding, Haoliang Fan, Chen Li, Yunle Meng |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Synucleinopathies animal diseases Primary Cell Culture Nuclear receptor related-1 protein Inflammation Exosomes Toxicology Hippocampus Methamphetamine Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Nuclear Receptor Subfamily 4 Group A Member 2 medicine Animals Humans Neurons biology Neurotoxicity General Medicine Meth medicine.disease Coculture Techniques Microvesicles nervous system diseases Cell biology Mice Inbred C57BL 030104 developmental biology nervous system chemistry Cell culture Astrocytes alpha-Synuclein biology.protein Cytokines Central Nervous System Stimulants Neurotoxicity Syndromes medicine.symptom Injections Intraperitoneal 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Toxicology Letters. 331:188-199 |
| ISSN: | 0378-4274 |
| DOI: | 10.1016/j.toxlet.2020.06.016 |
| Popis: | Methamphetamine (METH) is a highly addictive psychostimulant drug whose abuse can cause many health complications. Our previous studies have shown that METH exposure increases α-synuclein (α-syn) expression. Recently, it was shown that α-syn could be transferred from neurons to astrocytes via exosomes. However, the specific role of astrocytes in α-syn pathology involved in METH neurotoxicity remains unclear. The objective of this study was to determine whether exosomes derived from METH-treated neurons contain pathological α-syn and test the hypothesis that exosomes can transfer pathological α-syn from neurons to astrocytes. To this end, using animal and cell line coculture models, we show that exosomes isolated from METH-treated SH-SY5Y cells contained pathological α-syn. Furthermore, the addition of METH exosomes to the medium of primary cultured astrocytes induced α-syn aggregation and inflammatory responses in astrocytes. Then, we evaluated changes in nuclear receptor related 1 protein (Nurr1) expression and the levels of inflammatory cytokines in primary cultured astrocytes exposed to METH or α-syn. We found that METH or α-syn exposure decreased Nurr1 expression and increased proinflammatory cytokine expression in astrocytes. Our results indicate that α-syn can be transferred from neuronal cells to astrocytes through exosomes. When internalized α-syn accumulated in astrocytes, the cells produced inflammatory responses. Nurr1 may play a crucial role in this process and could be a therapeutic target for inflammatory damage caused by METH. |
| Databáze: | OpenAIRE |
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