Inflammatory neuronal loss in the substantia nigra induced by systemic lipopolysaccharide is prevented by knockout of the P2Y6 receptor in mice
| Autor: | Guy C. Brown, Jacob M Dundee, Francesca W. van Tartwijk, Anna Vilalta, Mar Puigdellívol, Stefan Milde, Tamara C. Hornik |
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| Přispěvatelé: | Brown, Guy C [0000-0002-3610-1730], Apollo - University of Cambridge Repository, Brown, Guy C. [0000-0002-3610-1730] |
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Male Parkinson's disease Malalties cerebrals PC12 Cells Brain stem Phagoptosis Mice Neuroinflammation Malaltia de Parkinson Cells Cultured Cell Line Transformed Mice Knockout Neurons biology Microglia Endotoxines General Neuroscience Neurodegeneration Substantia Nigra medicine.anatomical_structure Neurology Mort cel·lular Brain diseases medicine.symptom Cell death medicine.medical_specialty Micròglia Immunology Short Report P2Y6R Substantia nigra Inflammation Cellular and Molecular Neuroscience Organ Culture Techniques Phagocytosis Internal medicine medicine Animals RC346-429 Tronc de l'encèfal Tyrosine hydroxylase business.industry Receptors Purinergic P2 Dopaminergic Neurons medicine.disease Rats Endotoxins Mice Inbred C57BL Endocrinology nervous system biology.protein Parkinson’s disease Neurology. Diseases of the nervous system NeuN business |
| Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 18, Iss 1, Pp 1-9 (2021) Dipòsit Digital de la UB Universidad de Barcelona |
| DOI: | 10.17863/cam.76422 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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