scholarly journals A paternal methyl donor depleted diet leads to increased anxiety- and depression-like behavior in adult rat offspring

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Chelsea R. McCoy ◽  
Nateka L. Jackson ◽  
Rachel L. Brewer ◽  
Mohamad M. Moughnyeh ◽  
Daniel L. Smith ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Line ◽  
Emotional Health ◽  
Forced Swim Test ◽  
Emotional Behavior ◽  
Male Rats ◽  
Anxiety And Depression ◽  
Intergenerational Effects ◽  
Methyl Donor ◽  
Adult Rat

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.

scholarly journals Adult Male Rats Show Resilience to Adolescent Bisphenol A Effects on Hormonal and Behavioral Responses While Co-Exposure With Hop Extracts Supports Synergistic Actions

2021 ◽  
Vol 3 ◽  
Author(s):  
Alexandre Morin ◽  
Lise Van de Beeck ◽  
Emmanuelle Person ◽  
Helene Plamondon
Keyword(s):  
Bisphenol A ◽  
Corn Oil ◽  
Forced Swim Test ◽  
Behavioral Responses ◽  
Emotional Behavior ◽  
Male Rats ◽  
Brain Maturation ◽  
Male Wistar Rats ◽  
Adolescence Period ◽  
The Impact

The adolescence period, marked by sexual and brain maturation, has shown sensitivity to various environmental disruptors. Exposure to the xenoestrogen bisphenol A (BPA) is known to alter physiological and behavioral responses although its role at this critical period remains largely unknown. Recent research further suggests biochemical and genomic effects of BPA to be mitigated by various natural compounds, while effects on behavior have not been examined. This study aimed to characterize (1) the effects of dietary BPA during adolescence on endogenous corticosterone (CORT) secretion, emotional behavior, and testosterone (T) in adulthood, and (2) the impact of combined exposure to BPA with hop extracts (Hop), a phytoestrogen with anxiolytic properties. To do so, four groups of male Wistar rats [postnatal day (PND) 28] were administered corn oil (control), BPA (40 mg/kg), hops (40 mg/kg), or BPA-hops by oral gavage for 21 days (PND 28–48). Blood droplets collected on PND 28, 48, and 71 served to measure CORT and T changes. As adults, rats were tested in the elevated plus maze (EPM), the social interaction test, and the forced swim test. Our findings demonstrated elevated anxiety and a trend toward depressive-like behaviors in BPA- compared to hops-exposed rats. However, BPA intake had no impact on basal CORT levels, or adulthood T secretion and sociability. Of note, BPA's anxiogenic effect manifested through decreased EPM open arm entries was abolished by hops co-supplementation. Together, our observations suggest the adolescence period to be less sensitive to deleterious effects of BPA than what has been reported upon gestational and perinatal exposure.

scholarly journals The anxiolytic and antidepressant effect of Buxus hyrcana in the pentylenetetrazole kindled rat

2021 ◽  
Vol 72 (3) ◽  
pp. 3075
Author(s):  
V AZIZI ◽  
F ALLAHYARI ◽  
A HOSSEINI
Keyword(s):  
Oxidative Stress ◽  
Negative Impact ◽  
Forced Swim Test ◽  
Chemical Substance ◽  
The Body ◽  
Male Rats ◽  
Anxiety And Depression ◽  
Antidepressant Effect ◽  
Rotarod Test ◽  
Immobility Time

Pentylenetetrazole (PTZ) is a chemical substance which largely used for induction of seizure and epilepsy in the animal model, and it can also, disrupts free radicals balance and causes oxidative stress in the body with a negative impact on behavioral statuses like anxiety and depression. In this study, the medicinal plant Buxus hyrcana, was used to evaluate its effect on oxidative stress, anxiety and depression caused by PTZ in the rat. Twenty-four male rats were randomly allocated to 4 groups: control negative under treatment with PTZ (sub-threshold dose 35 mg/kg for one month), control positive under treatment with phenobarbital (PB-30 mg/kg), and two PTZ groups under treatment with B. hyrcana extract (BHE-300, and -600 mg/kg). For anxiety parameters, the elevated plus maze (EPM) was used. The forced swim test (FST) and rotarod test were employed to assess the antidepressant and balance potential, respectively. After behavioral evaluation, rats were anesthetized, brains were removed, and following preparation of brain homogenates, oxidative stress was evaluated using specified methods. BHE administered at the doses of 300, and 600 mg/kg, reduced immobility time in the FST exerting antidepressant-like activity. In the EPM test, BHE at the same doses, produced the anxiolytic-like effect. Also, the rats which received BHE had a significant improvement in rotarod test in contrast to control groups. In addition, brain catalase activity and superoxide dismutase level were significantly greater versus PTZ group BHE-300 treated PTZ group was significantly lower and. BHE could prevent anxiety and depression and ameliorate oxidative stress in PTZ-kindled rats.

Maternal anxiety and depression in pregnancy and DNA methylation of the NR3C1 glucocorticoid receptor gene

Epigenomics ◽  
2020 ◽  
Author(s):  
Alexandra E Dereix ◽  
Rachel Ledyard ◽  
Allyson M Redhunt ◽  
Tessa R Bloomquist ◽  
Kasey JM Brennan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Depressive Symptoms ◽  
Trait Anxiety ◽  
Cpg Island ◽  
Depression Scale ◽  
Maternal Anxiety ◽  
Anxiety And Depression ◽  
Pregnancy Anxiety ◽  
Glucocorticoid Receptor Gene ◽  
Island Shore

Aim: To quantify associations of anxiety and depression during pregnancy with differential cord blood DNA methylation of the glucorticoid receptor ( NR3C1). Materials & methods: Pregnancy anxiety, trait anxiety and depressive symptoms were collected using the Pregnancy Related Anxiety Scale, State-Trait Anxiety Index and Edinburgh Postnatal Depression Scale, respectively. NR3C1 methylation was determined at four methylation sites. Results: DNA methylation of CpG 1 in the NR3C1 CpG island shore was higher in infants born to women with high pregnancy anxiety (β 2.54, 95% CI: 0.49–4.58) and trait anxiety (β 1.68, 95% CI: 0.14–3.22). No significant association was found between depressive symptoms and NR3C1 methylation. Conclusion: We found that maternal anxiety was associated with increased NR3C1 CpG island shore methylation.

scholarly journals Methyl donor micronutrients, CD40-ligand methylation and disease activity in systemic lupus erythematosus: A cross-sectional association study

Lupus ◽  
2021 ◽  
pp. 096120332110345
Author(s):  
Stefan Vordenbäumen ◽  
Alexander Sokolowski ◽  
Anna Rosenbaum ◽  
Claudia Gebhard ◽  
Johanna Raithel ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
T Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cd40 Ligand ◽  
Systemic Lupus ◽  
Methyl Donors ◽  
Methyl Donor ◽  
The Mean

Objective Hypomethylation of CD40-ligand (CD40L) in T-cells is associated with increased disease activity in systemic lupus erythematosus (SLE). We therefore investigated possible associations of dietary methyl donors and products with CD40L methylation status in SLE. Methods Food frequency questionnaires were employed to calculate methyl donor micronutrients in 61 female SLE patients (age 45.7 ± 12.0 years, disease duration 16.2 ± 8.4 years) and compared to methylation levels of previously identified key DNA methylation sites (CpG17 and CpG22) within CD40L promotor of T-cells using quantitative DNA methylation analysis on the EpiTYPER mass spectrometry platform. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Linear regression modelling was used. P values were adjusted according to Benjamini & Hochberg. Results Amongst the micronutrients assessed (g per day), methionine and cysteine were associated with methylation of CpG17 (β = 5.0 (95%CI: 0.6-9.4), p = 0.04; and β = 2.4 (0.6-4.1), p = 0.02, respectively). Methionine, choline, and cysteine were additionally associated with the mean methylation of the entire CD40L (β = 9.5 (1.0-18.0), p = 0.04; β = 1.6 (0.4-3.0), p = 0.04; and β = 4.3 (0.9-7.7), p = 0.02, respectively). Associations of the SLEDAI with hypomethylation were confirmed for CpG17 (β=-32.6 (-60.6 to -4.6), p = 0.04) and CpG22 (β=-38.3 (-61.2 to -15.4), p = 0.004), but not the mean methylation of CD40L. Dietary products with the highest impact on methylation included meat, ice cream, white bread, and cooked potatoes. Conclusions Dietary methyl donors may influence DNA methylation levels and thereby disease activity in SLE.

scholarly journals DNA Methyltransferase 3A Is Involved in the Sustained Effects of Chronic Stress on Synaptic Functions and Behaviors

2020 ◽  
Author(s):  
Jing Wei ◽  
Jia Cheng ◽  
Nicholas J Waddell ◽  
Zi-Jun Wang ◽  
Xiaodong Pang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Epigenetic Modification ◽  
Substantial Reduction ◽  
Dna Methyltransferases ◽  
Male Rats ◽  
Neural Pathways ◽  
Dnmt Inhibitors ◽  
Synaptic Functions

Abstract Emerging evidence suggests that epigenetic mechanisms regulate aberrant gene transcription in stress-associated mental disorders. However, it remains to be elucidated about the role of DNA methylation and its catalyzing enzymes, DNA methyltransferases (DNMTs), in this process. Here, we found that male rats exposed to chronic (2-week) unpredictable stress exhibited a substantial reduction of Dnmt3a after stress cessation in the prefrontal cortex (PFC), a key target region of stress. Treatment of unstressed control rats with DNMT inhibitors recapitulated the effect of chronic unpredictable stress on decreased AMPAR expression and function in PFC. In contrast, overexpression of Dnmt3a in PFC of stressed animals prevented the loss of glutamatergic responses. Moreover, the stress-induced behavioral abnormalities, including the impaired recognition memory, heightened aggression, and hyperlocomotion, were partially attenuated by Dnmt3a expression in PFC of stressed animals. Finally, we found that there were genome-wide DNA methylation changes and transcriptome alterations in PFC of stressed rats, both of which were enriched at several neural pathways, including glutamatergic synapse and microtubule-associated protein kinase signaling. These results have therefore recognized the potential role of DNA epigenetic modification in stress-induced disturbance of synaptic functions and cognitive and emotional processes.

scholarly journals Stress Modifies the Expression of Glucocorticoid-Responsive Genes by Acting at Epigenetic Levels in the Rat Prefrontal Cortex: Modulatory Activity of Lurasidone

2021 ◽  
Vol 22 (12) ◽  
pp. 6197
Author(s):  
Paola Brivio ◽  
Giulia Sbrini ◽  
Letizia Tarantini ◽  
Chiara Parravicini ◽  
Piotr Gruca ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chronic Stress ◽  
Chronic Mild Stress ◽  
Male Rats ◽  
Mild Stress ◽  
Experimental Conditions ◽  
Glucocorticoid Responsive Element ◽  
Responsive Element

Epigenetics is one of the mechanisms by which environmental factors can alter brain function and may contribute to central nervous system disorders. Alterations of DNA methylation and miRNA expression can induce long-lasting changes in neurobiological processes. Hence, we investigated the effect of chronic stress, by employing the chronic mild stress (CMS) and the chronic restraint stress protocol, in adult male rats, on the glucocorticoid receptor (GR) function. We focused on DNA methylation specifically in the proximity of the glucocorticoid responsive element (GRE) of the GR responsive genes Gadd45β, Sgk1, and Gilz and on selected miRNA targeting these genes. Moreover, we assessed the role of the antipsychotic lurasidone in modulating these alterations. Chronic stress downregulated Gadd45β and Gilz gene expression and lurasidone normalized the Gadd45β modification. At the epigenetic level, CMS induced hypermethylation of the GRE of Gadd45β gene, an effect prevented by lurasidone treatment. These stress-induced alterations were still present even after a period of rest from stress, indicating the enduring nature of such changes. However, the contribution of miRNA to the alterations in gene expression was moderate in our experimental conditions. Our results demonstrated that chronic stress mainly affects Gadd45β expression and methylation, effects that are prolonged over time, suggesting that stress leads to changes in DNA methylation that last also after the cessation of stress procedure, and that lurasidone is a modifier of such mechanisms.

scholarly journals Epigenetic marking and repression of porcine endogenous retroviruses

2013 ◽  
Vol 94 (5) ◽  
pp. 960-970 ◽  
Author(s):  
Gernot Wolf ◽  
Anders Lade Nielsen ◽  
Jacob Giehm Mikkelsen ◽  
Finn Skou Pedersen
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Germ Line ◽  
Mammalian Species ◽  
Histone Deacetylation ◽  
Endogenous Retroviruses ◽  
Primer Binding Site ◽  
Retroviral Transduction ◽  
Embryonic Germ Cells ◽  
Epigenetic Repression

Endogenous retroviruses (ERVs) are remnants of retroviral germ line infections and have been identified in all mammals investigated so far. Although the majority of ERVs are degenerated, some mammalian species, such as mice and pigs, carry replication-competent ERVs capable of forming infectious viral particles. In mice, ERVs are silenced by DNA methylation and histone modifications and some exogenous retroviruses were shown to be transcriptionally repressed after integration by a primer-binding site (PBS) targeting mechanism. However, epigenetic repression of porcine ERVs (PERVs) has remained largely unexplored so far. In this study, we screened the pig genome for PERVs using LTRharvest, a tool for de novo detection of ERVs, and investigated various aspects of epigenetic repression of three unrelated PERV families. We found that these PERV families are differentially up- or downregulated upon chemical inhibition of DNA methylation and histone deacetylation in cultured porcine cells. Furthermore, chromatin immunoprecipitation analysis revealed repressive histone methylation marks at PERV loci in primary porcine embryonic germ cells and immortalized embryonic kidney cells. PERV elements belonging to the PERV-γ1 family, which is the only known PERV family that has remained active up to the present, were marked by significantly higher levels of histone methylations than PERV-γ2 and PERV-β3 proviruses. Finally, we tested three PERV-associated PBS sequences for repression activity in murine and porcine cells using retroviral transduction experiments and showed that none of these PBS sequences induced immediate transcriptional silencing in the tested primary porcine cells.

scholarly journals Maternal Melatonin Therapy Attenuates Methyl-Donor Diet-Induced Programmed Hypertension in Male Adult Rat Offspring

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1407 ◽  
Author(s):  
You-Lin Tain ◽  
Julie Chan ◽  
Chien-Te Lee ◽  
Chien-Ning Hsu
Keyword(s):  
Methylation Status ◽  
Normal Diet ◽  
Male Offspring ◽  
Adult Offspring ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Deficient Diet ◽  
Male Adult ◽  
Methyl Donor ◽  
Adult Rat

Although pregnant women are advised to consume methyl-donor food, some reports suggest an adverse outcome. We investigated whether maternal melatonin therapy can prevent hypertension induced by a high methyl-donor diet. Female Sprague-Dawley rats received either a normal diet, a methyl-deficient diet (L-MD), or a high methyl-donor diet (H-MD) during gestation and lactation. Male offspring were assigned to four groups (n = 7–8/group): control, L-MD, H-MD, and H-MD rats were given melatonin (100 mg/L) with their drinking water throughout the period of pregnancy and lactation (H-MD+M). At 12 weeks of age, male offspring exposed to a L-MD or a H-MD diet developed programmed hypertension. Maternal melatonin therapy attenuated high methyl-donor diet-induced programmed hypertension. A maternal L-MD diet and H-MD diet caused respectively 938 and 806 renal transcripts to be modified in adult offspring. The protective effects of melatonin against programmed hypertension relate to reduced oxidative stress, increased urinary NO2− level, and reduced renal expression of sodium transporters. A H-MD or L-MD diet may upset the balance of methylation status, leading to alterations of renal transcriptome and programmed hypertension. A better understanding of reprogramming effects of melatonin might aid in developing a therapeutic strategy for the prevention of hypertension in adult offspring exposed to an excessive maternal methyl-supplemented diet.

scholarly journals Особливості масометричних показників та морфологічних змін головного мозку статевозрілих щурів в умовах впливу на організм сульфатів міді, цинку та заліза

2015 ◽  
Author(s):  
А. М. Романюк ◽  
Г. Ю Будко
Keyword(s):  
Copper Sulfate ◽  
Morphological Changes ◽  
The Body ◽  
Male Rats ◽  
Relative Mass ◽  
Adult Rat ◽  
Applied Anatomy ◽  
Adult Rat Brain ◽  
Long Acting ◽  
The Brain

ОСОБЛИВОСТІ МАСОМЕТРИЧНИХ ПОКАЗНИКІВ ТА МОРФОЛОГІЧНИХ ЗМІН ГОЛОВНОГО МОЗКУ СТАТЕВОЗРІЛИХ ЩУРІВ В УМОВАХ ВПЛИВУ НА ОРГАНІЗМ СУЛЬФАТІВ МІДІ, ЦИНКУ ТА ЗАЛІЗА - З метою вивчення масометричних показників щурів та їх головного мозку за умов довготривалої дії (упродовж 90 діб) на організм сульфатів міді, цинку та заліза було проведено експеримент на 48 білих статевозрілих щурах-самцях масою 200-250 г віком 5-7 місяців. Застосовували анатомічні, статистичні та загальноприйняті методики мікроанатомічного методу дослідження. Встановлено, що комбінований вплив на організм сульфатів міді цинку та заліза чинить на головний мозок досить виражений токсичний ефект, що негативно позначається на масометричних показниках загальної маси щурів та маси головного мозку. Це свідчить про розвиток у головному мозку явищ гострого набряку з ознаками геморагічної інфільтрації. Ступінь вираження набряку зростає та досягає максимальних показників наприкінці експерименту.<br />ОСОБЕННОСТИ МАСОМЕТРИЧЕСКИХ ПОКАЗАТЕЛЕЙ И МОРФОЛОГИЧЕСКИХ ИЗМЕНЕНИЙ ГОЛОВНОГО МОЗГА ПОЛОВОЗРЕЛЫХ КРЫС В УСЛОВИЯХ ВОЗДЕЙСТВИЯ НА ОРГАНИЗМ СУЛЬФАТОВ МЕДИ, ЦИНКА И ЖЕЛЕЗА - С целью изучения масометрических показателей крыс и их головного мозга в условиях длительного действия (в течение 90 суток) на организм сульфатов меди, цинка и железа был проведен эксперимент на 48 белых половозрелых крысах-самцах массой 200250 г в возрасте 5-7 месяцев. Применялись анатомические, статистические и общепринятые методики микроанатомического метода исследования. Установлено, что комбинированное воздействие на организм сульфатов меди и цинка и железа оказывает на мозг достаточно выразительный токсический эффект, что отрицательно сказывается на массометрических показателях общего веса крыс и веса головного мозга. Это свидетельствует о развитии в головном мозге явлений острого отека с признаками геморрагической инфильтрации, степень выраженности которого максимальна в конце эксперимента.<br />FEATURES OF MASS INDICES AND MORPHOLOGICAL CHANGES IN ADULT RAT BRAIN UNDER THE INFLUENCE ON THE BODY OF COPPER SULFATE, ZINC AND IRON - To study the performance of rats and their mass brain in long acting (for 90 days) on the body of copper sulfate, zinc and iron, an experiment was conducted on 48 white adult male rats weighing 200-250 gram, aged 5-7 months. There was applied anatomy, statistics and conventional techniques microanatomical research method. It was established that the combined effect on the body of copper and zinc sulphates and iron in the brain has enough expressive toxicity, which affects performance on the total weight of the rats and brain weight. This testifies to the development of brain edema, acute phenomena with signs of hemorrhagic infiltration. The severity of edema increases and reaches maximum performance at the end of the experiment.<br />Ключові слова: головний мозок, солі важких металів, відносна маса, коефіцієнт цефалізації.<br />Ключевые слова: головной мозг, соли тяжелых металлов, относительная масса, коэффициент цефа- лизации.<br />Key words: brain, salts of heavy metals, relative mass, ratio cephalization.

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