期刊
PLOS ONE
卷 12, 期 10, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0185989
关键词
-
资金
- Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain [PI2014/06]
The role of astrocytes in Parkinson's disease is still not well understood. This work studied the astrocytic response to the dopaminergic denervation. Rats were injected in the lateral ventricles with 6-hydroxydopamine (25 mu g), inducing a dopaminergic denervation of the striatum not accompanied by non-selective tissue damage. The dopaminergic debris were found within spheroids (free-spheroids) which retained some proteins of dopaminergic neurons (e. g., tyrosine hydroxylase, the dopamine transporter protein, and APP) but not others (e.g., a-synuclein). Free-spheroids showed the initial (LC3-autophagosomes) but not the late (Lamp1/Lamp2-lysosomes) components of autophagy (incomplete autophagy), preparing their autophagosomes for an external phagocytosis (accumulation of phosphatidylserine). Free-spheroids were penetrated by astrocyte processes (fenestrated-spheroids) which made them immunoreactive for GFAP and S100 beta, and which had some elements needed to continue the debris degradation (Lamp1/Lamp2). Finally, proteins normally found in neurons (TH, DAT and a-synuclein) were observed within astrocytes 2-5 days after the dopaminergic degeneration, suggesting that the intracellular contents of degenerated cells had been transferred to astrocytes. Taken together, present data suggest phagocytosis as a physiological role of striatal astrocytes, a role which could be critical for cleaning striatal debris during the initial stages of Parkinson's disease.
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