Matches in SemOpenAlex for { <https://semopenalex.org/work/W630040753> ?p ?o ?g. }
- W630040753 abstract "Neurotransmitter dysregulation and reactive oxygen species (ROS) are a hallmark of neurodegenerative disease. Microglia, the immune cells of the CNS, express three NADPH oxidase isoforms (Nox1, Nox2 and Nox4), which produce superoxide that is used as an intracellular signalling molecule, mediating the production of neurotoxic and neurotrophic factors. Microglia also express a range of neurotransmitter receptors, enabling them to respond to physiological and pathological levels of neurotransmitters. As both microglial superoxide production and neurotransmitter dysregulation are common to many neurodegenerative conditions, the interaction between microglial neurotransmitter receptor modulation and NADPH oxidase activation was investigated.Superoxide production was assessed in primary and BV2 microglia using flow cytometry, HPLC, fluorescence microscopy, and a colorometric assay. Glutamate (1 μM), GABA (100 μM) or BzATP (250 μM) induced NADPH oxidase derived superoxide production. Furthermore, antagonism of the group I mGluRs induced Nox1 and Nox2 dependent superoxide production through PKC / PI3-K pathways and p44/42ERK activation. Activation of mGluR3 induced Nox2 and Nox4 activation in a p44/42ERK and p38MAPK dependent manner, whilst activation of the group III mGluRs induced Nox2 and Nox4 activation dependent on p38MAPK signalling. Microglial NMDA receptor activation promoted superoxide production that was dependent on p38MAPK activation. Modulation of the microglial glutamate receptors mediated protection of cerebellar granule neurons, as deomstrated using microglial conditioned media assays. Activation of the microglial GABAA receptor induced Nox1 activation through PKC and p38MAPK signalling which mediated TNFα release and neurotoxicity, whilst P2Y2/4 receptor activation mediated Nox1 activation through PI3-K and p38MAPK with neurotoxic consequences. The findings in this thesis show that microglial Nox2 and Nox4 activation has neuroprotective consequences, whereas microglial Nox1 activation mediates neurotoxicity. Modulation of the microglial neurotransmitter receptors therefore has ramifications for the survival of neurons in degenerative diseases, which could have important consequences for the production of future therapies for neurodegenerative conditions." @default.
- W630040753 created "2016-06-24" @default.
- W630040753 creator A5015131248 @default.
- W630040753 date "2012-01-28" @default.
- W630040753 modified "2023-09-28" @default.
- W630040753 title "Regulation of the microglial NADPH oxidase by neurotransmitters: implications for microglial – neuronal interactions" @default.
- W630040753 cites W103992419 @default.
- W630040753 cites W1256450896 @default.
- W630040753 cites W138509909 @default.
- W630040753 cites W143011653 @default.
- W630040753 cites W1454820827 @default.
- W630040753 cites W1484832749 @default.
- W630040753 cites W1487068141 @default.
- W630040753 cites W1495997476 @default.
- W630040753 cites W1500418512 @default.
- W630040753 cites W1502292420 @default.
- W630040753 cites W1503375802 @default.
- W630040753 cites W1504584187 @default.
- W630040753 cites W1505719764 @default.
- W630040753 cites W1510592624 @default.
- W630040753 cites W1519347646 @default.
- W630040753 cites W1519821638 @default.
- W630040753 cites W1522823711 @default.
- W630040753 cites W1524281376 @default.
- W630040753 cites W1536598983 @default.
- W630040753 cites W1537179351 @default.
- W630040753 cites W1540192329 @default.
- W630040753 cites W1548706173 @default.
- W630040753 cites W1550838463 @default.
- W630040753 cites W1558113022 @default.
- W630040753 cites W1559776259 @default.
- W630040753 cites W1568529372 @default.
- W630040753 cites W1569931447 @default.
- W630040753 cites W1573008536 @default.
- W630040753 cites W1576211545 @default.
- W630040753 cites W1584960502 @default.
- W630040753 cites W1587530349 @default.
- W630040753 cites W1591044893 @default.
- W630040753 cites W1591766297 @default.
- W630040753 cites W1592375995 @default.
- W630040753 cites W1597609025 @default.
- W630040753 cites W159824969 @default.
- W630040753 cites W1598718102 @default.
- W630040753 cites W1598922101 @default.
- W630040753 cites W1613451007 @default.
- W630040753 cites W1613771675 @default.
- W630040753 cites W1666261349 @default.
- W630040753 cites W1668456947 @default.
- W630040753 cites W1709163017 @default.
- W630040753 cites W1724950598 @default.
- W630040753 cites W1749116795 @default.
- W630040753 cites W1764067125 @default.
- W630040753 cites W1810573536 @default.
- W630040753 cites W1818767073 @default.
- W630040753 cites W1854163003 @default.
- W630040753 cites W1874751834 @default.
- W630040753 cites W1878700164 @default.
- W630040753 cites W1884006126 @default.
- W630040753 cites W1891696008 @default.
- W630040753 cites W1892698707 @default.
- W630040753 cites W1901115290 @default.
- W630040753 cites W1915946375 @default.
- W630040753 cites W1935475606 @default.
- W630040753 cites W1947551305 @default.
- W630040753 cites W1964041350 @default.
- W630040753 cites W1966367296 @default.
- W630040753 cites W1966851460 @default.
- W630040753 cites W1967173409 @default.
- W630040753 cites W1967720787 @default.
- W630040753 cites W1967751412 @default.
- W630040753 cites W1967811402 @default.
- W630040753 cites W1968619160 @default.
- W630040753 cites W1969176034 @default.
- W630040753 cites W1969307826 @default.
- W630040753 cites W1969505763 @default.
- W630040753 cites W1969616726 @default.
- W630040753 cites W1970157716 @default.
- W630040753 cites W1970684883 @default.
- W630040753 cites W1971026392 @default.
- W630040753 cites W1971202292 @default.
- W630040753 cites W1971556924 @default.
- W630040753 cites W1971701992 @default.
- W630040753 cites W1972222177 @default.
- W630040753 cites W1972317764 @default.
- W630040753 cites W1973489898 @default.
- W630040753 cites W1973531915 @default.
- W630040753 cites W1974284351 @default.
- W630040753 cites W1974643497 @default.
- W630040753 cites W1974657272 @default.
- W630040753 cites W1975802409 @default.
- W630040753 cites W1976881265 @default.
- W630040753 cites W1977378846 @default.
- W630040753 cites W1977899668 @default.
- W630040753 cites W1978450544 @default.
- W630040753 cites W1978658307 @default.
- W630040753 cites W1978902908 @default.
- W630040753 cites W1979867410 @default.
- W630040753 cites W1980166477 @default.
- W630040753 cites W1980447537 @default.
- W630040753 cites W1981396411 @default.