Academic Journal
Computer models predict differential dendritic vulnerability with ischemia and spreading depression.
| Τίτλος: | Computer models predict differential dendritic vulnerability with ischemia and spreading depression. |
|---|---|
| Συγγραφείς: | Newton AJH; Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, United States of America.; Department of Physiology and Pharmacology, SUNY Downstate Health Sciences University, Brooklyn, New York, United States of America., Lytton WW; Department of Physiology and Pharmacology, SUNY Downstate Health Sciences University, Brooklyn, New York, United States of America.; Department of Neurology, Kings County Hospital Center, Brooklyn, New York, United States of America., DiStasio M; Department of Pathology, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, Connecticut, United States of America.; Wu Tsai Institute, Yale University, New Haven, Connecticut, United States of America., McDougal RA; Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, United States of America.; Wu Tsai Institute, Yale University, New Haven, Connecticut, United States of America.; Department of Biomedical Informatics and Data Science, Yale School of Medicine, New Haven, Connecticut, United States of America.; Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, United States of America.; Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut, United States of America. |
| Πηγή: | PLoS computational biology [PLoS Comput Biol] 2026 Sep 08; Vol. 22 (9), pp. e1014701. Date of Electronic Publication: 2026 Sep 08 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article; Research Support, N.I.H., Extramural |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238922 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7358 (Electronic) Linking ISSN: 1553734X NLM ISO Abbreviation: PLoS Comput Biol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: San Francisco, CA : Public Library of Science, [2005]- |
| Ιατρικοί όροι (MeSH): | Dendrites*/physiology , Dendrites*/metabolism , Cortical Spreading Depression*/physiology , Brain Ischemia*/physiopathology , Brain Ischemia*/metabolism , Models, Neurological*, Pyramidal Cells/physiology ; Calcium/metabolism ; Potassium/metabolism ; CA1 Region, Hippocampal/physiopathology ; Animals ; Computer Simulation ; Computational Biology ; Humans |
| Περίληψη: | Ischemia, whether abrupt or chronic, limits ATP production and disrupts ATP-dependent homeostatic mechanisms, leading to alterations in both intracellular and extracellular ion concentrations. Inadequate neuronal ATP triggers K+ release and increased extracellular K+ depolarizes neurons, leading to additional K+ release; this positive feedback phenomenon is known as spreading depolarization (SD). When the depolarizing effects are strong enough, the cells undergo depolarization blockade, known as spreading depression. Excess extracellular K+ increases energy demand from the Na+-K+ pump, producing a pathological confluence of increased demand with reduced delivery of energy. The resulting changes have profound effects at subcellular, cellular, and network scales of brain function. We hypothesized that consequences of ischemic or SD homeostatic failure would differ on the subcellular scale, with differences between disjunct dendritic regions of a hippocampal CA1 pyramidal neuron. To evaluate the interplay between morphology and ion concentrations, we used a mechanistic simulation incorporating neuronal morphology, pumps, exchangers, voltage-, and Ca2+-sensitive ion channels. In both cases, calcium accumulation was greatest in the basal dendrites, suggesting these dendrites would show the greatest effects of excitotoxicity. By contrast, in ischemia, but not in SD, distal apical dendrites were exposed to greater intracellular chloride concentrations, which may lead to dendritic beading. (Copyright: © 2026 Newton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
| Competing Interests: | The authors have declared that no competing interests exist. |
| Σχόλια: | Update of: bioRxiv. 2025 Sep 24:2025.09.22.677786. doi: 10.1101/2025.09.22.677786.. (PMID: 41040194) |
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| Grant Information: | R01 MH086638 United States MH NIMH NIH HHS |
| Substance Nomenclature: | SY7Q814VUP (Calcium) RWP5GA015D (Potassium) |
| Entry Date(s): | Date Created: 20260908 Date Completed: 20260911 Latest Revision: 20260915 |
| Update Code: | 20260915 |
| PubMed Central ID: | PMC13568529 |
| DOI: | 10.1371/journal.pcbi.1014701 |
| PMID: | 42709853 |
| Βάση Δεδομένων: | MEDLINE |
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