Effects of hyperglycemia and aging on nuclear sirtuins and DNA damage of mouse hepatocytes

Hyperglycemia, like aging, induces chromatin remodeling in mouse hepatocytes in comparison to normoglycemia and younger age, respectively. Changes in glucose metabolism also affect the action and expression of sirtuins, promoting changes in chromatin conformation and dynamics. Here we investigate the abundance and activity of the nuclear sirtuins Sirt1, Sirt6, and Sirt7 in mouse hepatocytes in association with specific histone acetylation, DNA damage, and the activation of nucleolar organizing regions (NORs) in hyperglycemic nonobese diabetic (NOD) and old normoglycemic BALB/c mouse strains. Higher levels of Sirt1 and PGC-1α and increased expression of gluconeogenesis pathway genes are found in the hyperglycemic NOD mice. Increased Sirt6 abundance is found in the hyperglycemic NOD mice, which might increase DNA damage repair. With aging, lower Sirt1 abundance and activity, increased acetylated histone modifications and Sirt7 levels, and NOR methylation are found. Thus, whereas in normal aging cell metabolism is reduced, in the diabetic mice a compensatory mechanism may elevate Sirt1 and Sirt6 levels, increasing gluconeogenesis and DNA repair from the oxidative damage caused by hyperglycemia. Therefore understanding the regulation of epigenetic factors in diabetes and aging is crucial for the development of new therapeutic approaches that could prevent diseases and improve quality of life.

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Nonobese Diabetic (NOD) Mice Lack a Protective B-Cell Response against the “Nonlethal” Plasmodium yoelii 17XNL Malaria Protozoan

Malaria Research and Treatment ◽

10.1155/2016/6132734 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9

Author(s):

Mirian Mendoza ◽

Luis Pow Sang ◽

Qi Qiu ◽

Sofia Casares ◽

Teodor-D. Brumeanu

Keyword(s):

B Cell ◽

Nod Mice ◽

Treg Cells ◽

Plasmodium Yoelii ◽

Mouse Strains ◽

Nonobese Diabetic ◽

Blood Stage Infection ◽

Protective Antibodies ◽

Antibody Secretion

Background. Plasmodium yoelii 17XNL is a nonlethal malaria strain in mice of different genetic backgrounds including the C57BL/6 mice (I-Ab/I-Enull) used in this study as a control strain. We have compared the trends of blood stage infection with the nonlethal murine strain of P. yoelii 17XNL malaria protozoan in immunocompetent Nonobese Diabetic (NOD) mice prone to type 1 diabetes (T1D) and C57BL/6 mice (control mice) that are not prone to T1D and self-cure the P. yoelii 17XNL infection. Prediabetic NOD mice could not mount a protective antibody response to the P. yoelii 17XNL-infected red blood cells (iRBCs), and they all succumbed shortly after infection. Our data suggest that the lack of anti-P. yoelii 17XNL-iRBCs protective antibodies in NOD mice is a result of parasite-induced, Foxp3+ T regulatory (Treg) cells able to suppress the parasite-specific antibody secretion. Conclusions. The NOD mouse model may help in identifying new mechanisms of B-cell evasion by malaria parasites. It may also serve as a more accurate tool for testing antimalaria therapeutics due to the lack of interference with a preexistent self-curing mechanism present in other mouse strains.

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Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior

eLife ◽

10.7554/elife.13442 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 118

Author(s):

Mar Gacias ◽

Sevasti Gaspari ◽

Patricia-Mae G Santos ◽

Sabrina Tamburini ◽

Monica Andrade ◽

...

Keyword(s):

Gene Expression ◽

Prefrontal Cortex ◽

Social Behavior ◽

Gut Microbiota ◽

Nod Mice ◽

Mouse Strains ◽

Social Avoidance ◽

Nonobese Diabetic ◽

Gene Environment ◽

Transcriptional Changes

Gene-environment interactions impact the development of neuropsychiatric disorders, but the relative contributions are unclear. Here, we identify gut microbiota as sufficient to induce depressive-like behaviors in genetically distinct mouse strains. Daily gavage of vehicle (dH2O) in nonobese diabetic (NOD) mice induced a social avoidance behavior that was not observed in C57BL/6 mice. This was not observed in NOD animals with depleted microbiota via oral administration of antibiotics. Transfer of intestinal microbiota, including members of the Clostridiales, Lachnospiraceae and Ruminococcaceae, from vehicle-gavaged NOD donors to microbiota-depleted C57BL/6 recipients was sufficient to induce social avoidance and change gene expression and myelination in the prefrontal cortex. Metabolomic analysis identified increased cresol levels in these mice, and exposure of cultured oligodendrocytes to this metabolite prevented myelin gene expression and differentiation. Our results thus demonstrate that the gut microbiota modifies the synthesis of key metabolites affecting gene expression in the prefrontal cortex, thereby modulating social behavior.

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Postnatal Hematopoiesis and Gut Microbiota in NOD Mice Deviate from C57BL/6 Mice

Journal of Diabetes Research ◽

10.1155/2016/6321980 ◽

2016 ◽

Vol 2016 ◽

pp. 1-15 ◽

Cited By ~ 4

Author(s):

Dina Silke Malling Damlund ◽

Stine Broeng Metzdorff ◽

Jane Preuss Hasselby ◽

Maria Wiese ◽

Mia Lundsager ◽

...

Keyword(s):

Gut Microbiota ◽

Adaptive Immunity ◽

Early Life ◽

Autoimmune Diabetes ◽

Nod Mice ◽

Mouse Strains ◽

Newborn Mice ◽

Nonobese Diabetic ◽

Splenic Cell ◽

Cell Profile

Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate from another much used mouse strain, C57BL/6, with respect to postnatal microbiota and/or hematopoiesis and compared this in newborn mice of dams housed under the same conditions. A distinct bacteria profile rich instaphylococciwas found at postnatal days (PND) 1–4 in NOD mice. Furthermore, a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression ofReg3gandMuc2in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface in NOD compared to C57BL/6 mice.

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Strain-Dependent Migration of CD4 and CD8 Lymphocyte Subsets to Lymph Nodes in NOD (Nonobese Diabetic) and Control Mice

Developmental Immunology ◽

10.1155/1994/32820 ◽

1994 ◽

Vol 3 (4) ◽

pp. 273-282

Author(s):

Christelle Faveeuw ◽

Marie-Claude Gagnerault ◽

Françoise Lepault

Keyword(s):

Nod Mice ◽

Lymphoid Cells ◽

The Other ◽

T Cell Subsets ◽

Mouse Strains ◽

Cd4 Cells ◽

Cd8 Cells ◽

Nonobese Diabetic ◽

Other Hand

Subpopulations of lymphoid cells were compared with respect to their ability to migrate into peripheral lymphoid organs of nonobese diabetic (NOD) mice and various strains of control mice. In short-term,in vivohoming studies, no major differences in the pattern of homing of B and T cells were observed among all mouse strains studied. On the other hand, CD4 cells localized consistently more efficiently than CD8 cells in both PP and LN of adult NOD and BALB/c mice, whereas both populations migrated roughly equivalently in LN of adult DBA/2, CBA, and C57BL/6 mice. No age-dependent differences in the homing of CD4 and CD8 cells were observed in BALB/c mice. On the contrary, in 2-week-old NOD mice, CD4 and CD8 cells migrated equally well. The preferential entry of CD4 cells in adult NOD and BALB/c did not result from increased blood transit time of CD8 cells. On the other hand, the preferential migration of CD8 cells was observed in the liver, whereas the two T-cell subsets migrated equally well in the lungs. The differences in the homing characteristics of CD4 and CD8 cells among NOD, BALB/c, and C57BL/6 mice were not related to modifications in the level of expression of adhesion molecules such as MEL-14, LFA-1, and Pgp-1.

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