Seizure and redox rescue in a model of glucose transport deficiency DOI Creative Commons
Jay S. Coggan, Polina Shichkova, Henry Markram

et al.

PLoS Computational Biology, Journal Year: 2025, Volume and Issue: 21(4), P. e1012959 - e1012959

Published: April 4, 2025

Disruptions of energy supply to the brain are associated with many neurodegenerative pathologies and difficult study due numerous interlinked metabolic pathways. We explored effects diminished on metabolism using a computational model neuro-glia-vasculature ensemble, in form neuron, an astrocyte local blood supply. As case study, we investigated glucose transporter type-1 deficiency syndrome (GLUT1-DS), childhood affliction characterized by impaired utilization phenotypes including seizures. Compared neurons, astrocytes exhibited markedly higher metabolite concentration variabilities for all but few redox species. This effect could signal role absorbing shock nutrient fluctuations. Redox balances were disrupted GLUT1-DS lower levels reducing equivalent carriers NADH ATP. The best non-glucose or pharmacotherapies re-establishing normalcy involved lactate, keto-diet (β-hydroxybutyrate), NAD Q10 supplementation, suggesting possible sparing mechanism. seizures resulted from after-discharge neuronal firing caused post-stimulus ATP reductions Na + /K -ATPase, which can be rescued restoring either normal relatively small increases

Language: Английский

Seizure and redox rescue in a model of glucose transport deficiency DOI Creative Commons
Jay S. Coggan, Polina Shichkova, Henry Markram

et al.

PLoS Computational Biology, Journal Year: 2025, Volume and Issue: 21(4), P. e1012959 - e1012959

Published: April 4, 2025

Disruptions of energy supply to the brain are associated with many neurodegenerative pathologies and difficult study due numerous interlinked metabolic pathways. We explored effects diminished on metabolism using a computational model neuro-glia-vasculature ensemble, in form neuron, an astrocyte local blood supply. As case study, we investigated glucose transporter type-1 deficiency syndrome (GLUT1-DS), childhood affliction characterized by impaired utilization phenotypes including seizures. Compared neurons, astrocytes exhibited markedly higher metabolite concentration variabilities for all but few redox species. This effect could signal role absorbing shock nutrient fluctuations. Redox balances were disrupted GLUT1-DS lower levels reducing equivalent carriers NADH ATP. The best non-glucose or pharmacotherapies re-establishing normalcy involved lactate, keto-diet (β-hydroxybutyrate), NAD Q10 supplementation, suggesting possible sparing mechanism. seizures resulted from after-discharge neuronal firing caused post-stimulus ATP reductions Na + /K -ATPase, which can be rescued restoring either normal relatively small increases

Language: Английский

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