Hyperammonemia alters glycinergic neurotransmission and modulation of the glutamate-nitric oxide-cGMP pathway by extracellular glycine in cerebellum in vivo
Autor: | Vicente Felipo, Lucas Taoro-Gonzalez, Andrea Cabrera-Pastor |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty hyperammonemia Glycine Glutamic Acid Biology Neurotransmission Nitric Oxide NMDA receptors Synaptic Transmission Biochemistry glycinergic neurotrans-mission 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine nitric oxide Cerebellum Internal medicine medicine Animals Hyperammonemia Rats Wistar Cyclic GMP Glycine receptor Dose-Response Relationship Drug glycine receptors Glutamate receptor Extracellular Fluid Glutamic acid Strychnine medicine.disease Rats Cell biology cGMP 030104 developmental biology Endocrinology chemistry NMDA receptor Signal transduction 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | JOURNAL OF NEUROCHEMISTRY r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) instname r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) |
ISSN: | 0022-3042 |
Popis: | The glutamate-nitric oxide (NO)-cGMP pathway modulates some forms of learning. How glycine modulates this pathway is unclear. Glycine could modulate the pathway biphasically, enhancing its function through NMDA receptor activation or reducing it through glycine receptor activation. Chronic hyperammonemia impairs the glutamate-NO-cGMP pathway in the cerebellum and induces cognitive impairment. The possible alterations in hyperammonemia of glycinergic neurotransmission and of glutamate-NO-cGMP pathway modulation by glycine remain unknown. The aims were to assess, by in vivo microdialysis in cerebellum: (i) the effects of different glycine concentrations, administered through the microdialysis probe, on the glutamate-NO-cGMP pathway function; (ii) the effects of tonic glycine receptors activation on the pathway function, by blocking them with strychnine; (iii) whether hyperammonemia alters the pathway modulation by glycine; (iv) and whether hyperammonemia alters extracellular glycine concentration and/or glycine receptor membrane expression. In control rats, low glycine levels reduce the pathway function, likely by activating glycine receptors, while 20 μM glycine enhances the pathway function, likely by enhancing NMDA receptor activation. In hyperammonemic rats, glycine did not reduce the pathway function, but enhanced it when administered at 1-20 μM. Hyperammonemia reduces extracellular glycine concentration by approximately 50% and glycine receptor membrane expression. However, tonic glycine receptor activation seems to be enhanced in hyperammonemic rats, as indicated by the larger increase in extracellular cGMP induced by strychnine. These data show that glycine modulates the glutamate-NO-cGMP pathway biphasically and that hyperammonemia strongly alters glycinergic neurotransmission and modulation by glycine of the glutamate-NO-cGMP pathway. These alterations may contribute to the cerebellar aspects of cognitive alterations in hyperammonemia. The findings reported in this study show that hyperammonemia alters glycinergic neurotransmission and the glutamate-NO-cGMP pathway modulation by glycine. In control rats, low glycine levels reduced the pathway function, likely by activating glycine receptors, while 20 μM glycine enhanced the pathway, likely by enhancing NMDA receptor activation. In hyperammonemic rats, glycine (administered at 1-20 μM) enhances the pathway, likely by activating NMDA receptors. |
Databáze: | OpenAIRE |
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