The impact of the ‘Western Diet’ on emotional, social and cognitive behaviours as revealed by a study on conventional and serotonin transporter-deficient mice

Hypoxic pulmonary vasoconstriction (HPV) is a physiological vasomotor response that maintains systemic oxygenation by matching perfusion to ventilation during alveolar hypoxia. Although mitochondria appear to play an essential role in HPV, the impact of mitochondrial dysfunction on HPV remains incompletely defined. Mice lacking the mitochondrial complex I (CI) subunit Ndufs4 ( Ndufs4−/−) develop a fatal progressive encephalopathy and serve as a model for Leigh syndrome, the most common mitochondrial disease in children. Breathing normobaric 11% O2 prevents neurological disease and improves survival in Ndufs4−/− mice. In this study, we found that either genetic Ndufs4 deficiency or pharmacological inhibition of CI using piericidin A impaired the ability of left mainstem bronchus occlusion (LMBO) to induce HPV. In mice breathing air, the partial pressure of arterial oxygen during LMBO was lower in Ndufs4−/− and in piericidin A-treated Ndufs4+/+ mice than in respective controls. Impairment of HPV in Ndufs4−/− mice was not a result of nonspecific dysfunction of the pulmonary vascular contractile apparatus or pulmonary inflammation. In Ndufs4-deficient mice, 3 wk of breathing 11% O2 restored HPV in response to LMBO. When compared with Ndufs4−/− mice breathing air, chronic hypoxia improved systemic oxygenation during LMBO. The results of this study show that, when breathing air, mice with a congenital Ndufs4 deficiency or chemically inhibited CI function have impaired HPV. Our study raises the possibility that patients with inborn errors of mitochondrial function may also have defects in HPV.

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TP53INP1 deficiency maintains murine B lymphopoiesis in aged bone marrow through redox-controlled IL-7R/STAT5 signaling

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1809980116 ◽

2018 ◽

Vol 116 (1) ◽

pp. 211-216 ◽

Cited By ~ 2

Author(s):

Bochra Zidi ◽

Christelle Vincent-Fabert ◽

Laurent Pouyet ◽

Marion Seillier ◽

Amelle Vandevelde ◽

...

Keyword(s):

Oxidative Stress ◽

Bone Marrow ◽

B Cells ◽

B Cell ◽

Immune Cell ◽

B Lymphopoiesis ◽

Hematopoietic Stem ◽

Chronic Oxidative Stress ◽

The Impact ◽

Deficient Mice

Bone marrow (BM) produces all blood and immune cells deriving from hematopoietic stem cells (HSCs). The decrease of immune cell production during aging is one of the features of immunosenescence. The impact of redox dysregulation in BM aging is still poorly understood. Here we use TP53INP1-deficient (KO) mice endowed with chronic oxidative stress to assess the influence of aging-associated redox alterations in BM homeostasis. We show that TP53INP1 deletion has no impact on aging-related accumulation of HSCs. In contrast, the aging-related contraction of the lymphoid compartment is mitigated in TP53INP1 KO mice. B cells that accumulate in old KO BM are differentiating cells that can mature into functional B cells. Importantly, this phenotype results from B cell-intrinsic events associated with defective redox control. Finally, we show that oxidative stress in aged TP53INP1-deficient mice maintains STAT5 expression and activation in early B cells, driving high Pax5 expression, which provides a molecular mechanism for maintenance of B cell development upon aging.

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The interaction between serotonin transporter allelic variation and maternal care modulates sociability on Instagram

10.31234/osf.io/dkvnf ◽

2020 ◽

Cited By ~ 2

Author(s):

Andrea Bonassi ◽

Ilaria Cataldo ◽

Giulio Gabrieli ◽

Moses Tandiono ◽

Jia Nee Foo ◽

...

Keyword(s):

Serotonin Transporter ◽

Social Desirability ◽

Parental Bonding ◽

Serotonin Transporter Gene ◽

Individual Development ◽

Environment Interaction ◽

Transporter Gene ◽

Gene Environment ◽

The Impact ◽

Desirability Index

Human social interactions ensure recognition and approval from others, both in offline and online environments. This study applies a model from behavioural genetics on Instagram sociability to explore the impact of individual development on the behaviour on social networks.We hypothesize that sociable attitudes on Instagram resulted from an interaction between serotonin transporter gene alleles and the individual’s social relationship with caregivers. We assess environmental and genetic components of 57 Instagram users. The self-report questionnaire Parental Bonding Instrument is adopted to determine the quality of parental bonding. The number of posts, followed users (“followings”), and followers are collected from Instagram as measures of online social activity. Additionally, the ratio between the number of followers and followings (“Social Desirability Index”) was calculated to estimate the asymmetry of each user’s social network. Finally, buccal mucosa cell samples were acquired, and the polymorphism rs25531 (T/T homozygotes vs C-carriers) within the serotonin transporter gene was examined.In the preliminary analysis, we identified a gender effect on the number of followings. In line with our predictions, we specifically found a gene- environment interaction on the standardized Instagram “Social Desirability Index”: users with the genotype more sensitive to environmental influences (T/T homozygotes) showed a higher Instagram “Social Desirability Index” than non-sensitive ones (C-carriers) when they experienced positive maternal care.This result may contribute to the understanding of online social behaviour from a gene*environment perspective.

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Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity

Scientific Reports ◽

10.1038/s41598-021-96278-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Irene Cimino ◽

Debra Rimmington ◽

Y. C. Loraine Tung ◽

Katherine Lawler ◽

Pierre Larraufie ◽

...

Keyword(s):

Body Weight ◽

Energy Balance ◽

Food Intake ◽

Energy Expenditure ◽

Positive Energy ◽

Chow Diet ◽

Chromatin Regulator ◽

Positive Energy Balance ◽

The Impact ◽

Deficient Mice

AbstractNeuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat+/−p mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat+/−p mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetry system, food intake in Nnat+/−p mice was hypervariable, with some mice consuming more than twice the intake seen in wild type littermates. A hyperphagic response was also seen in Nnat+/−p mice in a second, non-home cage environment. An expected correlation between body weight and energy expenditure was seen, but corrections for the effects of positive energy balance and body weight greatly diminished the effect of neuronatin deficiency on energy expenditure. Male and female Nnat+/−p mice displayed subtle distinctions in the degree of variance body weight phenotype and food intake and further sexual dimorphism was reflected in different patterns of hypothalamic gene expression in Nnat+/−p mice. Loss of the imprinted gene Nnat is associated with a highly variable food intake, with the impact of this phenotype varying between genetically identical individuals.

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The Impact of Oxytocin on Neurite Outgrowth and Synaptic Proteins in Magel2-Deficient Mice

10.1101/2020.09.23.309955 ◽

2020 ◽

Author(s):

Alexandra Reichova ◽

Fabienne Schaller ◽

Stanislava Bukatova ◽

Zuzana Bacova ◽

Françoise Muscatelli ◽

...

Keyword(s):

Neurite Outgrowth ◽

Hippocampal Neurons ◽

Synapse Formation ◽

Primary Cultures ◽

Synaptic Proteins ◽

Neuronal Maturation ◽

Glutamatergic Synapses ◽

Associated Proteins ◽

The Impact ◽

Deficient Mice

AbstractOxytocin contributes to the regulation of cytoskeletal and synaptic proteins and could therefore affect the mechanisms of neurodevelopmental disorders, including autism. Both the Prader-Willi syndrome and Schaaf-Yang syndrome exhibit autistic symptoms involving the MAGEL2 gene. Magel2-deficient mice show a deficit in social behavior that is rescued following postnatal administration of oxytocin. Here, in Magel2-deficient mice, we showed that the neurite outgrowth of primary cultures of immature hippocampal neurons is reduced. Treatment with oxytocin, but not retinoic acid, reversed this abnormality. In the hippocampus of Magel2-deficient pups, we further demonstrated that several transcripts of neurite outgrowth-associated proteins, synaptic vesicle proteins, and cell-adhesion molecules are decreased. In the juvenile stage, when neurons are mature, normalization or even overexpression of most of these markers was observed, suggesting a delay in the neuronal maturation of Magel2-deficient pups. Moreover, we found reduced transcripts of the excitatory postsynaptic marker, Psd95 in the hippocampus and we observed a decrease of PSD95/VGLUT2 colocalization in the hippocampal CA1 and CA3 regions in Magel2-deficient mice, indicating a defect in glutamatergic synapses. Postnatal administration of oxytocin upregulated postsynaptic transcripts in pups; however, it did not restore the level of markers of glutamatergic synapses in Magel2-deficient mice. Overall, Magel2 deficiency leads to abnormal neurite outgrowth and reduced glutamatergic synapses during development, suggesting abnormal neuronal maturation. Oxytocin stimulates the expression of numerous genes involved in neurite outgrowth and synapse formation in early development stages. Postnatal oxytocin administration has a strong effect in development that should be considered for certain neuropsychiatric conditions in infancy.

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Abstract 152: Stat4 Deficiency limits the Development and Progression of Atherosclerosis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a152 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Paresa Taghavie-Moghadam ◽

Matthew Butcher ◽

Mark Kaplan ◽

Jerry Nadler ◽

Elena Galkina

Keyword(s):

T Cells ◽

B Cell ◽

Plaque Burden ◽

Chow Diet ◽

Th1 Cells ◽

Peripheral Tissues ◽

The Impact ◽

Deficient Mice

T helper 1 (Th1) cells constitute the majority of plaque infiltrating IFNγ+ T cells and play a pro-atherogenic role. Th1 cells are induced via IFNγ-dependent activation of T-box expressed in T cells (Tbet) and/or IL-12-dependent activation of signal transducer and activator of transcription 4 (Stat4). While the role of Tbet in atherosclerosis is established, the impact of the IL-12/Stat4-dependent pathway is not well defined. To address the role of Stat4 in atherosclerosis, we bred Stat4-deficient mice with Apolipoprotein E-deficient mice to generate Stat4-/-Apoe-/- mice. Deficiency of Stat4 resulted in approximately a 70% reduction in the plaque burden for 34 week old Stat4-/-Apoe-/- mice fed a chow diet and in 12 week old Stat4-/-Apoe-/- mice fed a western diet there was approximately a 40% reduction in plaque burden, both compared with diet matched Apoe-/- controls females (p<0.001). To assess the effect of Stat4 on Th1 and Treg cell differentiation, we performed an in vitro polarization assay. Deficiency of Stat4 reduced differentiation of IFNγ+ Th1 cells in Th1 conditions, but supported the induction of Tregs in Treg polarizing conditions, confirming the importance of Stat4 in regulating the Th1/Treg balance. In contrast to the in vitro results, we found no difference in the expression of both IFNγ and Foxp3 amongst Stat4-/-Apoe-/- and Apoe-/- lymph nodes and splenic CD4+ T cells; suggesting that additional cytokines in vivo may induce IFNγ+Th1 and inhibit Treg differentiation. Stat4 deficiency also resulted in increased splenic B cell numbers and a slight increase in B1a dependent T15/E06 mRNA expression. Stat4 is a powerful regulator of chemokine expression within peripheral tissues. Adoptively transferred Apoe-/- B cells and CD11b+ cells migrated more efficiently into Stat4-/-Apoe-/- aortas compared to Apoe-/- recipients. However, percentages of macrophages, as determined by CD11b+CD68+ were reduced within the spleens and aortas of Stat4-/-Apoe-/- mice as compared to Apoe-/- controls at steady state conditions. In conclusion, Stat4 deficiency results in reduced atherosclerosis via the modulation of B cell function and aortic leukocyte content.

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From the Table to the Tumor: The Role of Mediterranean and Western Dietary Patterns in Shifting Microbial-Mediated Signaling to Impact Breast Cancer Risk

Nutrients ◽

10.3390/nu11112565 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2565 ◽

Cited By ~ 8

Author(s):

Tiffany M. Newman ◽

Mara Z. Vitolins ◽

Katherine L. Cook

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Mediterranean Diet ◽

Dietary Patterns ◽

Gut Microbiome ◽

Western Diet ◽

Diet Pattern ◽

The Mediterranean ◽

The Impact

Diet is a modifiable component of lifestyle that could influence breast cancer development. The Mediterranean dietary pattern is considered one of the healthiest of all dietary patterns. Adherence to the Mediterranean diet protects against diabetes, cardiovascular disease, and cancer. Reported consumption of a Mediterranean diet pattern was associated with lower breast cancer risk for women with all subtypes of breast cancer, and a Western diet pattern was associated with greater risk. In this review, we contrast the available epidemiological breast cancer data, comparing the impact of consuming a Mediterranean diet to the Western diet. Furthermore, we will review the preclinical data highlighting the anticancer molecular mechanism of Mediterranean diet consumption in both cancer prevention and therapeutic outcomes. Diet composition is a major constituent shaping the gut microbiome. Distinct patterns of gut microbiota composition are associated with the habitual consumption of animal fats, high-fiber diets, and vegetable-based diets. We will review the impact of Mediterranean diet on the gut microbiome and inflammation. Outside of the gut, we recently demonstrated that Mediterranean diet consumption led to distinct microbiota shifts in the mammary gland tissue, suggesting possible anticancer effects by diet on breast-specific microbiome. Taken together, these data support the anti-breast-cancer impact of Mediterranean diet consumption.

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