Increased stress and altered expression of histone modifying enzymes in brain are associated with aberrant behaviour in vitamin B12 deficient female mice

2018 ◽  
Vol 23 (9) ◽  
pp. 714-723 ◽  
Author(s):  
Shampa Ghosh ◽  
Jitendra Kumar Sinha ◽  
Nitin Khandelwal ◽  
Sumana Chakravarty ◽  
Arvind Kumar ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Altered Expression ◽  
Female Mice ◽  
Aberrant Behaviour ◽  
Histone Modifying Enzymes

scholarly journals Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice

2013 ◽  
Vol 304 (12) ◽  
pp. E1321-E1330 ◽  
Author(s):  
Kazunari Nohara ◽  
Rizwana S. Waraich ◽  
Suhuan Liu ◽  
Mathieu Ferron ◽  
Aurélie Waget ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
Adult Female ◽  
Sympathetic Tone ◽  
Visceral Adiposity ◽  
Androgen Excess ◽  
Altered Expression ◽  
Female Mice ◽  
The Impact

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

scholarly journals A Dietary Vitamin B12 Deficiency Impairs Balance and Coordination After Ischemic Injury to the Sensorimotor Cortex in Adult Male and Female Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 932-932
Author(s):  
Gyllian Yahn ◽  
Brandi Wasek ◽  
Terry Bottiglieri ◽  
Nafisa Jadavji
Keyword(s):  
Risk Factor ◽  
Ischemic Stroke ◽  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
Stroke Outcome ◽  
Deficient Diet ◽  
Male And Female ◽  
Female Mice ◽  
B12 Deficiency ◽  
Total Homocysteine

Abstract Objectives The majority of the world's population is growing older, in 2000, 10% of the total population of the world was over 60 years old and is projected to increase to 21% by 2050. Brain vasculature is unique, and its aging has been scarcely investigated at the cellular, and molecular levels, as well as in the context of age-related comorbidities. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, the majority of older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin. Furthermore, a vitamin B12 deficiency results in elevated levels of homocysteine which is a risk factor for cardiovascular diseases, such as stroke. Using a mouse model system, the aim of this study was to understand the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in the brain. Methods At 10-weeks of age male and female C57Bl/6J mice were put on control (0.025 mg/kg of vitamin B12) or vitamin B12 deficient (0 mg/kg of vitamin B12) diets for 4-weeks prior to ischemic damage. At 14 weeks of age we induced ischemic stroke in the sensorimotor cortex using the photothrombosis model, all animals received damage. Animals continued on diets for 4 weeks after damage. At 18 weeks of age we assessed stroke outcome using the accelerating rotarod and forepaw placement task. After the collection of behavioral data, we euthanized animals and collected brain, blood, and liver tissue to assess histological and biochemical measurements. Plasma was used to measure total homocysteine and methylmalonic acid. Results All animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. Male and female mice maintained on a vitamin B12 deficient diet had impairments in balance and coordination on the accelerating rotarod compared to animals maintained on a control diet. Conclusions Vitamin B12 deficiency impacts motor function in older adult male and female mice. We are investigating damage volume and potential mechanisms within the damage brain tissue. Funding Sources Midwestern University Start-Up Funds.

scholarly journals Sirt1-PPARS Cross-Talk in Complex Metabolic Diseases and Inherited Disorders of the One Carbon Metabolism

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1882 ◽  
Author(s):  
Viola J. Kosgei ◽  
David Coelho ◽  
Rosa-Maria Guéant-Rodriguez ◽  
Jean-Louis Guéant
Keyword(s):  
Metabolic Syndrome ◽  
Vitamin B12 ◽  
Metabolic Diseases ◽  
Preclinical Study ◽  
Peroxisome Proliferator ◽  
Inherited Disorders ◽  
Peroxisome Proliferator Activated Receptor ◽  
Altered Expression ◽  
The Metabolic Syndrome ◽  
Pregnancy And Lactation

Sirtuin1 (Sirt1) has a NAD (+) binding domain and modulates the acetylation status of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and Fork Head Box O1 transcription factor (Foxo1) according to the nutritional status. Sirt1 is decreased in obese patients and increased in weight loss. Its decreased expression explains part of the pathomechanisms of the metabolic syndrome, diabetes mellitus type 2 (DT2), cardiovascular diseases and nonalcoholic liver disease. Sirt1 plays an important role in the differentiation of adipocytes and in insulin signaling regulated by Foxo1 and phosphatidylinositol 3′-kinase (PI3K) signaling. Its overexpression attenuates inflammation and macrophage infiltration induced by a high fat diet. Its decreased expression plays a prominent role in the heart, liver and brain of rat as manifestations of fetal programming produced by deficit in vitamin B12 and folate during pregnancy and lactation through imbalanced methylation/acetylation of PGC1α and altered expression and methylation of nuclear receptors. The decreased expression of Sirt1 produced by impaired cellular availability of vitamin B12 results from endoplasmic reticulum stress through subcellular mislocalization of ELAVL1/HuR protein that shuttles Sirt1 mRNA between the nucleus and cytoplasm. Preclinical and clinical studies of Sirt1 agonists have produced contrasted results in the treatment of the metabolic syndrome. A preclinical study has produced promising results in the treatment of inherited disorders of vitamin B12 metabolism.

scholarly journals Programming of Glucose Homeostasis by Developmental Exposure to Folic Acid and Vitamin B12 Imbalance in Female Mice

2013 ◽  
Vol 37 ◽  
pp. S70
Author(s):  
Jesse D. Olson ◽  
Rika E. Aleiunas ◽  
Melissa B. Glier ◽  
Abeer M. Aljaadi ◽  
Tim J. Green ◽  
...  
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Glucose Homeostasis ◽  
Developmental Exposure ◽  
Female Mice

scholarly journals Altered dietary ratio of folic acid and vitamin B12 during pregnancy influences the expression of imprinted H19/IGF2 locus in C57BL/6 mice

2021 ◽  
pp. 1-42
Author(s):  
Aatish Mahajan ◽  
Divika Sapehia ◽  
Beenish Rahat ◽  
Jyotdeep Kaur
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Serum Levels ◽  
Differentially Methylated Region ◽  
Imprinted Genes ◽  
Altered Expression ◽  
Fetal Tissues ◽  
B12 Deficiency ◽  
In Utero Development ◽  
Dietary Deficiency

Abstract Maternal folic acid and vitamin B12 (B12) status during pregnancy influence fetal growth. This study elucidated the effect of altered dietary ratio of folic acid and B12 on the regulation of H19/IGF2 locus in C57BL/6 mice. Female mice were fed diets with 9 combinations of folic acid and B12 for 4 weeks. They were mated and the offspring born (F1) were continued on the same diet for 6 weeks post-weaning and were allowed to mate. The placenta and fetal (F2) tissues were collected at day 20 of gestation. H19 overexpression observed under dietary deficiency of folate combined with normal B12 (BNFD) was associated with an increased expression of miR-675 in maternal and fetal tissues. Insulin-like growth factor 2 (IGF2), expression was decreased under folic acid deficient conditions combined with normal, deficient or over-supplemented state of B12 (BNFD, BDFD, BOFD) in fetal tissues along with B12 deficiency combined with normal folic acid (BDFN) in the placenta. The altered expression of imprinted genes under folic acid deficient conditions was related to decreased serum levels of folate and body weight (F1). Hypermethylation observed at the H19 differentially methylated region (DMR) (in BNFD) might be responsible for the decreased expression of IGF2 in female fetal tissues. IGF2 DMR2 was found to be hypomethylated and associated with low serum B12 levels with B12 deficiency in fetal tissues. Results suggest that the altered dietary ratio of folic acid and B12 affects the in-utero development of the fetus in association with altered epigenetic regulation of H19/IGF2 locus.

Abstract P807: Vitamin B12 Deficiency Impairs Balance and Coordination After Photothrombotic Damage to the Sensorimotor Cortex in Adult Male and Female Mice After Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Gyllian Yahn ◽  
Teodoro Bottiglieri ◽  
Brandi Wasek ◽  
Nafisa Jadavji
Keyword(s):  
Ischemic Stroke ◽  
Vitamin B12 ◽  
Control Diet ◽  
Vitamin B12 Deficiency ◽  
Stroke Outcome ◽  
Deficient Diet ◽  
Male And Female ◽  
Female Mice ◽  
B12 Deficiency ◽  
Total Homocysteine

Introduction: The majority of the world’s population is growing older, in 2000, 10% of the total population of the world was over 60 years old and is projected to increase to 21% by 2050. Brain vasculature is unique, and its aging has been scarcely investigated at the cellular, and molecular levels, as well as in the context of age-related comorbidities. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, the majority of older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin. Furthermore, a vitamin B12 deficiency results in elevated levels of homocysteine which is a risk factor for cardiovascular diseases, such as stroke. Using a mouse model system, the aim of this study was to understand the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in the brain. Hypothesis: Vitamin B12 deficient mice will exhibit worse stroke outcome compared to control diet mice through increased apoptosis. Methods: At 10-weeks of age male and female C57Bl/6J mice were put on control (0.025 mg/kg of vitamin B12) or vitamin B12 deficient (0 mg/kg of vitamin B12) diets for 4-weeks prior to ischemic damage. At 14 weeks of age we induced ischemic stroke in the sensorimotor cortex using the photothrombosis model, all animals received damage. Animals continued on diets for 4 weeks after damage. At 18 weeks of age we assessed stroke outcome using the accelerating rotarod and forepaw placement task. After the collection of behavioral data, we euthanized animals and collected brain and liver tissue to assess histological and biochemical measurements. Plasma was used to measure total homocysteine and methylmalonic acid. Results: All animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. Male and female mice maintained on a vitamin B12 deficient diet had impairments in balance and coordination on the accelerating rotarod compared to animals maintained on a control diet. Conclusions: Vitamin B12 deficiency impacts motor function in older adult male and female mice. We are investigating damage volume and potential mechanisms within the damage brain tissue.

Altered Expression of Insulin Signaling Proteins in Islets from T2DM Female Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 314-LB
Author(s):  
KORIE L. SONDGEROTH ◽  
KATHY LEPARD
Keyword(s):  
Insulin Signaling ◽  
Signaling Proteins ◽  
Altered Expression ◽  
Female Mice

scholarly journals Effect of imbalance in folate and vitamin B12 in maternal/parental diet on global methylation and regulatory miRNAs

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aatish Mahajan ◽  
Divika Sapehia ◽  
Shilpa Thakur ◽  
Palani Selvam Mohanraj ◽  
Rashmi Bagga ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Vitamin B12 ◽  
Dna Methyltransferases ◽  
Central Component ◽  
Global Methylation ◽  
Altered Expression ◽  
Carbon Carrier ◽  
B12 Deficiency ◽  
Folate And Vitamin B12 ◽  
F1 Generation

AbstractDNA methylation, a central component of the epigenetic network is altered in response to nutritional influences. In one-carbon cycle, folate acts as a one-carbon carrier and vitamin B12 acts as co-factor for the enzyme methionine synthase. Both folate and vitamin B12 are the important regulators of DNA methylation which play an important role in development in early life. Previous studies carried out in this regard have shown the individual effects of these vitamins but recently the focus has been to study the combined effects of both the vitamins during pregnancy. Therefore, this study was planned to elucidate the effect of the altered dietary ratio of folate and B12 on the expression of transporters, related miRNAs and DNA methylation in C57BL/6 mice. Female mice were fed diets with 9 combinations of folate and B12 for 4 weeks. They were mated and off-springs born (F1) were continued on the same diet for 6 weeks post-weaning. Maternal and fetal (F2) tissues were collected at day 20 of gestation. Deficient state of folate led to an increase in the expression of folate transporters in both F1 and F2 generations, however, B12 deficiency (BDFN) also led to an increase in the expression in both the generations. B12 transporters/proteins were found to be increased with B12 deficiency in F1 and F2 generations except for TC-II in the kidney which was found to be decreased in the F1 generation. miR-483 was found to be increased with all conditions of folate and B12 in both F1 and F2 generations, however, deficient conditions of B12 led to an increase in the expression of miR-221 in both F1 and F2 generations. The level of miR-133 was found to be increased in BDFN group in F1 generation however; in F2 generation the change in expression was tissue and sex-specific. Global DNA methylation was decreased with deficiency of both folate and B12 in maternal tissues (F1) but increased with folate deficiency in placenta (F1) and under all conditions in fetal tissues (F2). DNA methyltransferases were overall found to be increased with deficiency of folate and B12 in both F1 and F2 generations. Results suggest that the dietary ratio of folate and B12 resulted in altered expression of transporters, miRNAs, and genomic DNA methylation in association with DNMTs.

Sign in / Sign up

Export Citation Format

Share Document