Blocking glycine receptors reduces neuroinflammation and restores neurotransmission in cerebellum through ADAM17-TNFR1-NF-?ß pathway.
Por:
Arenas YM, Cabrera-Pastor A, Juciute N, Mora-Navarro E and Felipo V
Publicada:
11 sep 2020
Resumen:
Chronic hyperammonemia induces neuroinflammation in cerebellum, with glial activation and enhanced activation of the TNFR1-NF-kB-glutaminase-glutamate-GABA pathway. Hyperammonemia also increases glycinergic neurotransmission. These alterations contribute to cognitive and motor impairment. Activation of glycine receptors is reduced by extracellular cGMP, which levels are reduced in cerebellum of hyperammonemic rats in vivo. We hypothesized that enhanced glycinergic neurotransmission in hyperammonemic rats (1) contributes to induce neuroinflammation and glutamatergic and GABAergic neurotransmission alterations; (2) is a consequence of the reduced extracellular cGMP levels. The aims were to assess, in cerebellum of hyperammonemic rats, (a) whether blocking glycine receptors with the antagonist strychnine reduces neuroinflammation; (b) the cellular localization of glycine receptor; (c) the effects of blocking glycine receptors on the TNFR1-NF-kB-glutaminase-glutamate-GABA pathway and microglia activation; (d) whether adding extracellular cGMP reproduces the effects of strychnine.
Filiaciones:
:
Laboratory of Neurobiology, Príncipe Felipe Research Center Valencia, C/Eduardo Primo Yúfera 3, 46012, Valencia, Spain
:
Laboratory of Neurobiology, Príncipe Felipe Research Center Valencia, C/Eduardo Primo Yúfera 3, 46012, Valencia, Spain.
Laboratory of Neurological Impairment, Health Research Institute INCLIVA, 46010, Valencia, Spain.
Juciute N:
Laboratory of Neurobiology, Príncipe Felipe Research Center Valencia, C/Eduardo Primo Yúfera 3, 46012, Valencia, Spain
Mora-Navarro E:
Laboratory of Neurobiology, Príncipe Felipe Research Center Valencia, C/Eduardo Primo Yúfera 3, 46012, Valencia, Spain
:
Laboratory of Neurobiology, Príncipe Felipe Research Center Valencia, C/Eduardo Primo Yúfera 3, 46012, Valencia, Spain
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