Ahmed, Sadia and Travis, Sierrah D. and Díaz-Bahamonde, Francisca V. and Porter, Demisha D. L. and Henry, Sara N. and Mykins, Julia and Ravipati, Aditya and Booker, Aryn and Ju, Jing and Ding, Hanzhang and Ramesh, Ashwin K. and Pickrell, Alicia M. and Wang, Maosen and LaConte, Stephen and Howell, Brittany R. and Yuan, Lijuan and Morton, Paul D. (2021) Early Influences of Microbiota on White Matter Development in Germ-Free Piglets. Frontiers in Cellular Neuroscience, 15. ISSN 1662-5102
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Abstract
Abnormalities in the prefrontal cortex (PFC), as well as the underlying white matter (WM) tracts, lie at the intersection of many neurodevelopmental disorders. The influence of microorganisms on brain development has recently been brought into the clinical and research spotlight as alterations in commensal microbiota are implicated in such disorders, including autism spectrum disorders, schizophrenia, depression, and anxiety via the gut-brain axis. In addition, gut dysbiosis is common in preterm birth patients who often display diffuse WM injury and delayed WM maturation in critical tracts including those within the PFC and corpus callosum. Microbial colonization of the gut aligns with ongoing postnatal processes of oligodendrogenesis and the peak of brain myelination in humans; however, the influence of microbiota on gyral WM development remains elusive. Here, we develop and validate a neonatal germ-free swine model to address these issues, as piglets share key similarities in WM volume, developmental trajectories, and distribution to humans. We find significant region-specific reductions, and sexually dimorphic trends, in WM volume, oligodendrogenesis, and mature oligodendrocyte numbers in germ-free piglets during a key postnatal epoch of myelination. Our findings indicate that microbiota plays a critical role in promoting WM development during early life when the brain is vulnerable to environmental insults that can result in an array of disabilities manifesting later in life.
Item Type: | Article |
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Subjects: | Open Research Librarians > Medical Science |
Depositing User: | Unnamed user with email support@open.researchlibrarians.com |
Date Deposited: | 11 Apr 2023 07:40 |
Last Modified: | 17 May 2024 09:58 |
URI: | http://stm.e4journal.com/id/eprint/629 |