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Mangus, L. M.

Publications and source records attributed to Mangus, L. M..

2 recordsLinked to original sources

Variation in the Gut Microbiota of Common Marmosets: Differences with Colony of Origin and Integration

Characterization of the gut microbiome may aid understanding and management of natural and experimental disease states in research animals, thereby promoting reproducibility. In this study, the rectal bacterial communities of three separate common marmoset (Callithrix jacchus) breeding colonies were defined using 16S rRNA sequencing of rectal swab samples. Study animals originated from two German colonies and a United States colony (JHU). The two German cohorts, previously fed the same diet, were imported into the JHU facility; they were then isolated, transitioned onto JHU diet, and then moved into rooms housing JHU animals. To dissect the contributions of diet and integration in shaping the rectal bacterial community, samples were collected from German origin marmosets upon JHU arrival (baseline), following diet transition (100 d), and following cohousing (390 d). Baseline and 390 d samples were collected from stably maintained JHU marmosets. Bacterial community composition was distinct between all three cohorts at baseline, suggesting that factors other than primary diet confer significant differences between captive populations. Beta-diversity of the animals from the two German colonies converged by 100 d but remained distinct from JHU sample beta-diversity throughout the 390-d study, indicating that diet had greater influence on bacterial community composition than did housing animals within the same room. Our results demonstrate substantial differences in gut bacteria between different captive marmoset colonies, with persistence of these differences following husbandry standardization and housing integration. Goals of rigor and reproducibility in research underscore the need to consider microbial differences between marmosets of diverse origin. ImportanceCharacterizing gut microbial populations is expected to promote health and enhance research reproducibility in animal studies. As use of common marmosets as animal models of human diseases expands, evaluating the marmoset gut bacterial community will be critical for interpreting research findings, especially as marmosets are prone to gastrointestinal inflammation. In this study, using 16S rRNA sequencing of rectal swab samples, we compared bacterial community among three captive colonies of marmosets at baseline and following importation of cohorts from two of the colonies into the third colony. Diet history had sustained influence on bacterial community composition, while housing the animals within the same room over a period of eight months did not appear to be a major factor. These persistent differences in marmoset gut bacterial community highlight the need for careful consideration of animal origin as a variable in marmoset research studies.

microbiology

UPREGULATION OF SUPEROXIDE DISMUTASE 2 BY ASTROCYTES IN THE SIV/MACAQUE MODEL OF HIV-ASSOCIATED NEUROLOGIC DISEASE

HIV-associated neurocognitive disorders (HAND) remain prevalent despite implementation of antiretroviral therapy (ART). Development of HAND is linked to mitochondrial dysfunction and oxidative stress in the brain; therefore, upregulation of antioxidant defenses is critical to curtail neuronal damage. Superoxide dismutase 2 (SOD2) is a mitochondrial antioxidant enzyme essential for maintaining cellular viability. We hypothesized that SOD2 was upregulated during retroviral infection. Using a simian immunodeficiency virus (SIV)-infected macaque model of HIV, quantitative PCR showed elevated SOD2 mRNA in cortical gray (GM, 7.6-fold for SIV vs. uninfected) and white matter (WM, 77-fold for SIV vs. uninfected) during SIV infection. Further, SOD2 immunostaining was enhanced in GM and WM from SIV-infected animals. Double immunofluorescence labeling illustrated that SOD2 primarily co-localized with astrocyte marker glial fibrillary acidic protein (GFAP) in SIV-infected animals. Interestingly, in ART-treated SIV-infected animals, brain SOD2 RNA levels were similar to uninfected animals. Additionally, using principal component analysis in a transcriptomic approach, SOD2 and GFAP expression separated SIV-infected from uninfected brain tissue. Projection of these data into a HIV dataset revealed similar expression changes, thereby validating the clinical relevance. Together, our findings suggest that novel SOD2-enhancing therapies may delay the onset or reduce severity of HAND seen in ART-treated HIV-infected patients.

neuroscience