Effects of Prenatal Phthalate Exposure and Childhood Exercise on Maternal Behaviors in Female Rats at Postpartum: A Role of Oxtr Methylation in the Hypothalamus

Both the detrimental effect of prenatal exposure to di-(2-ethylhexyl)-phthalate (DEHP) and the beneficial effects of physical exercise on brain functions have been reported. The oxytocin pathway has been implicated in the onset of maternal behaviors. Epigenetic modification of the oxytocin receptor gene (OXTR) through DNA methylation has been associated with the pathogenesis of neuropsychiatric disorders. The purpose of this study was to investigate the effects of prenatal DEHP exposure on oxytocin-regulated maternal behaviors and to examine the protective effect of exercise. Pregnant rats (F0) were fed with vehicle or DEHP during gestation and the offspring females (F1) were assessed for their maternal behaviors by pup retrieval test at postpartum. The results showed that reduced pup retrieval activities without significant alteration of stress responses were observed in the prenatally DEHP-exposed females. Prenatal DEHP exposure decreased the expressions of oxytocin, Oxtr mRNA, and oxytocin receptor, and increased Oxtr methylation in the hypothalamus of postpartum female rats. There were no significant effects of exercise on behavioral, biochemical, and epigenetic measurements. These results suggest that prenatal DEHP exposure has a long-term adverse effect on maternal behaviors; Oxtr hyper-methylation may be a potential epigenetic mechanism for this alteration, which cannot be prevented by physical exercise during childhood.

Download Full-text

Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children

Psychological Medicine ◽

10.1017/s0033291720004353 ◽

2020 ◽

pp. 1-11

Author(s):

Lorenza Dall’ Aglio ◽

Jolien Rijlaarsdam ◽

Rosa H. Mulder ◽

Alexander Neumann ◽

Janine F. Felix ◽

...

Keyword(s):

Dna Methylation ◽

Stress Responses ◽

Association Studies ◽

Maternal Sensitivity ◽

Population Based ◽

Epigenetic Mechanism ◽

Developmental Problems ◽

Maternal Caregiving ◽

Typical Variation

Abstract Background Experimental work in animals has shown that DNA methylation (DNAm), an epigenetic mechanism regulating gene expression, is influenced by typical variation in maternal care. While emerging research in humans supports a similar association, studies to date have been limited to candidate gene and cross-sectional approaches, with a focus on extreme deviations in the caregiving environment. Methods Here, we explored the prospective association between typical variation in maternal sensitivity and offspring epigenome-wide DNAm, in a population-based cohort of children (N = 235). Maternal sensitivity was observed when children were 3- and 4-years-old. DNAm, quantified with the Infinium 450 K array, was extracted at age 6 (whole blood). The influence of methylation quantitative trait loci (mQTLs), DNAm at birth (cord blood), and confounders (socioeconomic status, maternal psychopathology) was considered in follow-up analyses. Results Genome-wide significant associations between maternal sensitivity and offspring DNAm were observed at 13 regions (p < 1.06 × 10−07), but not at single sites. Follow-up analyses indicated that associations at these regions were in part related to genetic factors, confounders, and baseline DNAm levels at birth, as evidenced by the presence of mQTLs at five regions and estimate attenuations. Robust associations with maternal sensitivity were found at four regions, annotated to ZBTB22, TAPBP, ZBTB12, and DOCK4. Conclusions These findings provide novel leads into the relationship between typical variation in maternal caregiving and offspring DNAm in humans, highlighting robust regions of associations, previously implicated in psychological and developmental problems, immune functioning, and stress responses.

Download Full-text

Predictive Metabolomics Evaluation of Nutrition-Modulated Metabolic Stress Responses in Human Blood Serum During the Early Recovery Phase of Strenuous Physical Exercise

Journal of Proteome Research ◽

10.1021/pr900081q ◽

2009 ◽

Vol 8 (6) ◽

pp. 2966-2977 ◽

Cited By ~ 79

Author(s):

Elin Chorell ◽

Thomas Moritz ◽

Stefan Branth ◽

Henrik Antti ◽

Michael B. Svensson

Keyword(s):

Physical Exercise ◽

Blood Serum ◽

Human Blood ◽

Stress Responses ◽

Metabolic Stress ◽

Recovery Phase ◽

Human Blood Serum ◽

Early Recovery ◽

Strenuous Physical Exercise ◽

Early Recovery Phase

Download Full-text

Effects of exercise on insulin distribution and action in testosterone-treated oophorectomized female rats

Journal of Applied Physiology ◽

10.1152/jappl.2000.88.6.2116 ◽

2000 ◽

Vol 88 (6) ◽

pp. 2116-2122 ◽

Cited By ~ 9

Author(s):

Maria Niklasson ◽

Peter Daneryd ◽

Peter Lönnroth ◽

Agneta Holmäng

Keyword(s):

Insulin Resistance ◽

Physical Exercise ◽

Insulin Action ◽

Female Rats ◽

Control Group ◽

Free Access ◽

Euglycemic Hyperinsulinemic Clamp ◽

Severe Insulin Resistance ◽

Ovx Rats ◽

Running Wheels

Administration of testosterone (T) to oophorectomized (Ovx) female rats is followed by severe insulin resistance, localized to postreceptor cellular events in the muscle. In this study, intervention by exercise was introduced to examine whether circulatory adaptations are involved in insulin resistance. Two groups of Ovx rats were studied: one group was given T (Ovx+T); another group had free access to running wheels (Ovx+T+Ex). In addition, one control group (sham operated) was studied. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp technique (submaximal) for 150 min. Muscle interstitial glucose and insulin concentrations were measured by microdialysis. The measurements showed that, in Ovx+T rats, the onset of insulin action was significantly ( P < 0.05) slower during the first 95 min of the clamp compared with that in Ovx+T+Ex and controls. Muscle interstitial concentrations of insulin but not glucose were lower in both Ovx+T and Ovx+T+Ex rats than in controls throughout the clamp. It was concluded that physical exercise prevented the slow onset of insulin action in Ovx+T rats without changing the distribution time of muscle interstitial insulin. The results indicate that hyperandrogenicity is characterized by delayed muscle insulin action. Physical exercise reverses these defects without any beneficial effect on muscle interstitial insulin concentrations.

Download Full-text

Proteomic Analysis of Cold Stress Responses in Banana Leaves

Journal of the American Society for Horticultural Science ◽

10.21273/jashs.140.3.214 ◽

2015 ◽

Vol 140 (3) ◽

pp. 214-222 ◽

Cited By ~ 9

Author(s):

Ren-jun Feng ◽

Li-li Zhang ◽

Jing-yi Wang ◽

Jin-mei Luo ◽

Ming Peng ◽

...

Keyword(s):

Protein Synthesis ◽

Energy Metabolism ◽

Cold Stress ◽

Stress Responses ◽

Southern China ◽

Epigenetic Modification ◽

Stress Conditions ◽

Ros Scavenging ◽

Two Dimensional Gel Electrophoresis ◽

Cold Temperatures

Cold stress is one of the most important environmental factors affecting crop growth and agricultural production. Induced changes of gene expression and metabolism are critical for plants responding and acclimating to cold stress. Banana (Musa sp.) is one of the most important food crops in the tropical and subtropical countries of the world. Banana, which originated from tropical regions, is sensitive to cold, which can result in serious losses in commercial banana production. To investigate the response of the banana to cold stress conditions, changes in protein expression were analyzed using a comparative proteomics approach. ‘Brazil’ banana (Musa acuminata AAA group) is a common banana cultivar in southern China. ‘Brazil’ banana plantlets were exposed to 5 °C for 24 hours and then total crude protein was extracted from treatment and control leaves by phenol extraction, separated with two-dimensional gel electrophoresis, and subsequently identified by mass spectrometry (MS). Out of the more than 400 protein spots reproducibly detected, only 41 protein spots exhibited a change in intensity by at least 2-fold, with 26 proteins increasing and 15 proteins decreasing expression. Of these, 28 differentially expressed proteins were identified by MS. The identified proteins, including well-known and novel cold-responsive proteins, are involved in several cellular processes, including antioxidation and antipathogen, photosynthesis, chaperones, protein synthesis, signal transduction, energy metabolism, and other cellular functions. Proteins related to antioxidation, pathogen resistance, molecular chaperones, and energy metabolism were up-regulated, and proteins related to ethylene synthesis, protein synthesis, and epigenetic modification were down-regulated in response to cold temperature treatment. The banana plantlets incubated at cold temperatures demonstrated major changes in increased reactive oxygen species (ROS) scavenging, defense against diseases, and energy supply. Increased antioxidation capability in banana was also discovered in plantain, which has greater cold tolerance than banana in response to cold stress conditions. Therefore, we hypothesized that an increased antioxidation ability could be a common characteristic of banana and plantain in response to cold stress conditions. These findings may provide a better understanding of the physiological processes of banana in response to cold stress conditions.

Download Full-text

Gating of the neuroendocrine stress responses by stressor salience in early lactating female rats is independent of infralimbic cortex activation and plasticity

Stress ◽

10.1080/10253890.2018.1434618 ◽

2018 ◽

Vol 21 (3) ◽

pp. 217-228 ◽

Cited By ~ 1

Author(s):

Katharina M. Hillerer ◽

Barbara Woodside ◽

Emily Parkinson ◽

Hong Long ◽

Silvanna Verlezza ◽

...

Keyword(s):

Stress Responses ◽

Female Rats ◽

Infralimbic Cortex

Download Full-text

Abstract WP153: Post-Stroke Physical Exercise Improves Cognition in Middle-Aged Female Rats

Stroke ◽

10.1161/str.51.suppl_1.wp153 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Sharnikha Saravanan ◽

Weizhao Zhao ◽

Kunjan R Dave ◽

Miguel A Perez-Pinzon ◽

Ami P Raval

Keyword(s):

Enzyme Activity ◽

Physical Exercise ◽

Cognitive Decline ◽

Fear Conditioning ◽

Enzyme Activities ◽

Female Rats ◽

Male Rats ◽

Mitochondrial Enzyme ◽

Post Stroke ◽

Activity Measurements

Background: A woman’s risk of a stroke increases exponentially following the onset of menopause, andpost-stroke cognitive decline is a significant consequence of stroke survivors. Our earlier study demonstrated that physical exercise (PE) reduced post-stroke brain injury and improved cognitive functions in male rats. The focus of our study is on the improvement of post-stroke cognitive function in female rats. Methods: Reproductively senescent Sprague-Dawley female rats were exposed to transient middle cerebral artery occlusion (tMCAO; 90 min) and randomly assigned to either PE or sham-PE groups. After 3-5 days, rats underwent sham-PE (0m/min speed) or PE (15m/min speed) for 30 mins either every day (continuous) or alternate day for five times on treadmill. The rats that underwent the alternate day paradigm were treated with ER-β agonist (DPN; 1mg/kg) or vehicle-DMSO immediately following PE/sham-PE sessions to determine the synergistic effect. Twenty-one days after the last PE/sham-PE, rats were tested for hippocampal-dependent contextual fear conditioning and freeze time was measured. Rat brains were processed for histology and infarct area was measured with MCID software. From a separate cohort of rat subjected to PE or sham-PE, brain tissue was harvested for various biochemical assays and mitochondrial enzyme activity measurements. Results: Post-tMCAO continuous PE did not reduce ischemic damage. However, alternate PE regimen with or without ER-β agonist reduced infract volume by 20% (p < 0.05) and 23% (p < 0.05), respectively as compared to no-PE. Similarly, alternate PE showed increased freezing on the second day of fear conditioning by 15% (p < 0.05), indicating improved spatial memory. Individual mitochondrial complex I, II, III and IV enzyme activity measurements demonstrated significant improvement in complex III-IV enzyme activities in the alternate PE treated group as compared to sham-PE. Conclusion: An alternate day PE paradigm and ER-β activation improves post-stroke mitochondrial enzyme activities and cognition in reproductively senescent female rats. Future studies delineating underlying mechanism could help identify therapies to prevent/reduce cognitive decline in menopausal female stroke patients.

Download Full-text

A chromatin modulator sustains self-renewal and enables differentiation of postnatal neural stem and progenitor cells

Journal of Molecular Cell Biology ◽

10.1093/jmcb/mjz036 ◽

2019 ◽

Vol 12 (1) ◽

pp. 4-16 ◽

Cited By ~ 4

Author(s):

Kushani Shah ◽

Gwendalyn D King ◽

Hao Jiang

Keyword(s):

Progenitor Cells ◽

Neural Progenitor Cells ◽

Epigenetic Modification ◽

Gene Activation ◽

The Self ◽

Epigenetic Mechanism ◽

H3k4 Methylation ◽

Self Renewal ◽

Stem And Progenitor Cells ◽

Human Neural Progenitor Cells

Abstract It remains unknown whether H3K4 methylation, an epigenetic modification associated with gene activation, regulates fate determination of the postnatal neural stem and progenitor cells (NSPCs). By inactivating the Dpy30 subunit of the major H3K4 methyltransferase complexes in specific regions of mouse brain, we demonstrate a crucial role of efficient H3K4 methylation in maintaining both the self-renewal and differentiation capacity of postnatal NSPCs. Dpy30 deficiency disrupts development of hippocampus and especially the dentate gyrus and subventricular zone, the major regions for postnatal NSC activities. Dpy30 is indispensable for sustaining the self-renewal and proliferation of NSPCs in a cell-intrinsic manner and also enables the differentiation of mouse and human neural progenitor cells to neuronal and glial lineages. Dpy30 directly regulates H3K4 methylation and the induction of several genes critical in neurogenesis. These findings link a prominent epigenetic mechanism of gene expression to the fundamental properties of NSPCs and may have implications in neurodevelopmental disorders.

Download Full-text

Postnatal Expression Patterns of Estrogen Receptor Subtypes and Choline Acetyltransferase in Different Regions of the Papez Circuit

Developmental Neuroscience ◽

10.1159/000502686 ◽

2019 ◽

Vol 41 (3-4) ◽

pp. 203-211 ◽

Cited By ~ 1

Author(s):

Yu-xiang Wang ◽

Lin Zhu ◽

Li-xia Li ◽

Hui-nan Xu ◽

Hong-gang Wang ◽

...

Keyword(s):

Estrogen Receptor ◽

Choline Acetyltransferase ◽

Brain Area ◽

Expression Patterns ◽

Female Rats ◽

Long Term Memory ◽

Receptor Subtypes ◽

Brain Functions ◽

Papez Circuit ◽

G Protein Coupled

The Papez circuit is crucial for several brain functions, including long-term memory and emotion. Estradiol modulates cognitive functions based on the expression pattern of its receptor subtypes including estrogen receptor (ER) α, β, and G protein-coupled receptor 30 (GPR30). Similarly, the activity in the cholinergic system correlates with several brain functions, such as learning and memory. In this study, we used immunofluorescence to examine the expression patterns of ERβ and Western blotting to analyze GPR30 and choline acetyltransferase (ChAT) expression, in different regions of the Papez circuit, including the prefrontal cortex, hippocampus, hypothalamus, anterior nucleus of the thalamus, and cingulum in female rats at postnatal days (PND) 1, 10, and 56. Our main finding was that the highest expression of ERβ and GPR30 was noted in each brain area of the Papez circuit in the PND1 rats, whereas the expression of ChAT was the highest in PND10 rats. These results provide vital information on the postnatal expression patterns of ER subtypes and ChAT in different regions of the Papez circuit.

Download Full-text