Scholarly Works, School of Neuroscience
Permanent URI for this collection
Research articles, presentations, and other scholarship
Browse
Browsing Scholarly Works, School of Neuroscience by Subject "0601 Biochemistry and Cell Biology"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- Early influences of microbiota on white matter development in germ-free pigletsAhmed, Sadia; Travis, Sierrah; Díaz-Bahamonde, Francisca; Porter, Demisha; Henry, Sara; Ravipati, Aditya; Booker, Aryn; Ding, Hanzhang; Ju, Jing; Ramesh, Ashwin; Pickrell, Alicia M.; Wang, Maosen; LaConte, Stephen M.; Howell, Brittany R.; Yuan, Lijuan; Morton, Paul D. (Frontiers, 2021-12-27)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.
- A paternal methyl donor depleted diet leads to increased anxiety- and depression-like behavior in adult rat offspringMcCoy, Chelsea R.; Jackson, Nateka L.; Brewer, Rachel L.; Moughnyeh, Mohamad M.; Smith, Daniel L.; Clinton, Sarah M. (Portland Press, 2018-08-31)Epigenetic mechanisms such as DNA methylation elicit lasting changes in gene expression and likely mediate gene–environment interactions that shape brain development, behavior, and emotional health. Myriad environmental factors influence DNA methylation, including methyl donor content in the paternal diet, could influence methylation in offspring via changes in the paternal germ line. The present study examines the effects of paternal methyl donor dietary deficiency on offspring’s emotional behaviors, including anxiety, social interaction, and depression-like behavior. We previously found that rats bred to display high levels of anxiety- and depression-like behavior exhibit diminished DNA methylation in the amygdala. We also observed that depleting dietary methyl donor content exacerbated the rats’ already high levels of anxiety- and depression-like behavior. Here we sought to determine whether paternal dietary methyl donor depletion elicits intergenerational effects on first generation (F1) offspring’s behavior (potentially triggering a similar increase in anxiety- and/or depression-like behavior). Thus, adult male rats prone to high anxiety/depression-like behavior, were fed either a methyl donor depleted (DEP) or control (CON) diet for 5 weeks prior to mating. They were paired with females and resultant F1 male offspring were subjected to a behavioral test battery in adulthood. F1-DEP offspring showed a similar behavioral profile to the F0 males, including greater depression-like behavior in the forced swim test (FST) and increased anxiety-like behavior in the open field test (OFT). Future work will interrogate molecular changes in the brains of F1 offspring that mediate these intergenerational effects of paternal methyl donor dietary content on offspring emotional behavior.