Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/186581
Title: Inflammatory neuronal loss in the substantia nigra induced by systemic lipopolysaccharide is prevented by knockout of the P2Y 6 receptor in mice
Author: Milde, Stefan
van Tartwijk, Francesca W.
Vilalta, Anna
Hornik, Tamara C.
Dundee, Jacob M.
Puigdellívol Cañadell, Mar
Brown, Guy C.
Keywords: Mort cel·lular
Micròglia
Malaltia de Parkinson
Tronc de l'encèfal
Malalties cerebrals
Endotoxines
Cell death
Microglia
Parkinson's disease
Brain stem
Brain diseases
Endotoxins
Issue Date: 11-Oct-2021
Publisher: BioMed Central
Abstract: Inflammation may contribute to multiple brain pathologies. One cause of inflammation is lipopolysaccharide/endotoxin (LPS), the levels of which are elevated in blood and/or brain during bacterial infections, gut dysfunction and neurodegenerative diseases, such as Parkinson's disease. How inflammation causes neuronal loss is unclear, but one potential mechanism is microglial phagocytosis of neurons, which is dependent on the microglial P2Y6 receptor. We investigated here whether the P2Y6 receptor was required for inflammatory neuronal loss. Intraperitoneal injection of LPS on 4 successive days resulted in specific loss of dopaminergic neurons (measured as cells staining with tyrosine hydroxylase or NeuN) in the substantia nigra of wild-type mice, but no neuronal loss in cortex or hippocampus. This supports the hypothesis that neuronal loss in Parkinson's disease may be driven by peripheral LPS. By contrast, there was no LPS-induced neuronal loss in P2Y6 receptor knockout mice. In vitro, LPS-induced microglial phagocytosis of cells was prevented by inhibition of the P2Y6 receptor, and LPS-induced neuronal loss was reduced in mixed glial-neuronal cultures from P2Y6 receptor knockout mice. This supports the hypothesis that microglial phagocytosis contributes to inflammatory neuronal loss, and can be prevented by blocking the P2Y6 receptor, suggesting that P2Y6 receptor antagonists might be used to prevent inflammatory neuronal loss in Parkinson's disease and other brain pathologies involving inflammatory neuronal loss.
Note: Reproducció del document publicat a: https://doi.org/10.1186/s12974-021-02280-2
It is part of: Journal of Neuroinflammation, 2021, vol. 18, num. 1, p. 225
URI: http://hdl.handle.net/2445/186581
Related resource: https://doi.org/10.1186/s12974-021-02280-2
ISSN: 1742-2094
Appears in Collections:Articles publicats en revistes (Biomedicina)

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