Impaired Complex I dysregulates neural/glial precursors and corpus callosum development revealing postnatal defects in Leigh syndrome mice.
| Title: | Impaired Complex I dysregulates neural/glial precursors and corpus callosum development revealing postnatal defects in Leigh syndrome mice. |
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| Authors: | Biswas SR; Translational Biology, Medicine, and Health Graduate Program, Virginia Polytechnic Institute and State University, Roanoke, VA, 24016, USA.; Tomsick PL; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA.; Kelly C; Translational Biology, Medicine, and Health Graduate Program, Virginia Polytechnic Institute and State University, Roanoke, VA, 24016, USA.; Lester BA; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA.; Milner JP; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA.; Henry SN; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA.; Soto Y; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA.; Brindley S; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA.; DeFoor N; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA.; Morton PD; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA. pmorton@vt.edu.; Pickrell AM; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA. alicia.pickrell@vt.edu. |
| Source: | EMBO molecular medicine [EMBO Mol Med] 2026 Feb; Vol. 18 (2), pp. 677-701. Date of Electronic Publication: 2025 Dec 22. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: EMBO Press Country of Publication: Germany NLM ID: 101487380 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1757-4684 (Electronic) Linking ISSN: 17574676 NLM ISO Abbreviation: EMBO Mol Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2024- : Heidelberg : EMBO Press; Original Publication: Chichester, West Sussex : Wiley-Blackwell |
| MeSH Terms: | Leigh Disease*/pathology ; Leigh Disease*/genetics ; Corpus Callosum*/pathology ; Corpus Callosum*/growth & development ; Neuroglia*/pathology ; Neural Stem Cells*/pathology ; Neural Stem Cells*/physiology ; Electron Transport Complex I*/metabolism ; Electron Transport Complex I*/genetics ; Electron Transport Complex I*/deficiency; Animals ; Mice ; Disease Models, Animal ; Cell Proliferation ; Humans |
| Abstract: | Leigh syndrome (LS) is a complex, genetic mitochondrial disorder defined by neurodegenerative phenotypes with pediatric manifestation. However, recent clinical studies report behavioral phenotypes in human LS patients that are more reminiscent of neurodevelopmental delays. To determine if disruptions in epochs of rapid brain growth during infancy precede the hallmark brain lesions that arise during childhood, we evaluated neural and glial precursor cellular dynamics in a mouse model of LS. Loss of Complex I significantly impacted neural stem cell proliferation, neuronal and oligodendroglial progeny, lineage progression, and displayed overt differences in specific brain regions across postnatal development. Our findings show that these disruptions in all categories occur specifically within the subventricular zone and corpus callosum prior to the age when these mice experience neurodegeneration. Given that LS is considered a neurodegenerative disease, we propose that there are neurodevelopmental signatures predating classic diagnosis in LS.; (© 2025. The Author(s).) |
| Competing Interests: | Disclosure and competing interests statement. The authors declare no competing interests. |
| Comments: | Update of: bioRxiv. 2025 May 16:2025.05.16.654318. doi: 10.1101/2025.05.16.654318.. (PMID: 40462991) |
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| Grant Information: | R01 ES035013 United States ES NIEHS NIH HHS; R35 GM142368 United States GM NIGMS NIH HHS; R01ES035013 HHS | National Institutes of Health (NIH); R35GM142368 HHS | National Institutes of Health (NIH) |
| Contributed Indexing: | Keywords: Corpus Callosum; Leigh Syndrome; Neural Stem Cells; Postnatal Neurogenesis; Subventricular Zone |
| Substance Nomenclature: | EC 7.1.1.2 (Electron Transport Complex I) |
| Entry Date(s): | Date Created: 20251222 Date Completed: 20260213 Latest Revision: 20260217 |
| Update Code: | 20260217 |
| PubMed Central ID: | PMC12905379 |
| DOI: | 10.1038/s44321-025-00367-4 |
| PMID: | 41429945 |
| Database: | MEDLINE |
Journal Article