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

Male Zucker diabetic fatty (mZDF) rats spontaneously develop type 2 diabetes, whereas females only become diabetic when fed a diabetogenic high-fat diet (high-fat-fed female ZDF rat, HF-fZDF). The aim of this study was to investigate if differences in liver functions could provide clues to this sex difference. Non-diabetic obese fZDF rats were compared with either mZDF or HF-fZDF regarding hepatic molecular profiles, to single out those components that might be protective in the females. High-fat feeding in fZDF led to enhanced weight gain, increased blood glucose and insulin levels, reduced insulin sensitivity and a trend towards reduced glucose tolerance, indicative of a prediabetic state. mZDF rats were diabetic, with low levels of insulin, high levels of glucose, reduced insulin sensitivity and impaired glucose tolerance. Transcript profiling and capillary electrophoresis time-of-flight mass spectrometry were used to indentify hepatic transcripts and metabolites that might be related to this. Many diet-induced alterations in transcript and metabolite levels in female rats were towards a ‘male-like’ phenotype, including reduced lipogenesis, increased fatty acid (FA) oxidation and increased oxidative stress responses. Alterations detected at the level of hepatic metabolites, indicated lower capacity for glutathione (GSH) production in male rats, and higher GSH turnover in females. Taken together, this could be interpreted as if anabolic pathways involving lipogenesis and lipid output might limit the degree of FA oxidation and oxidative stress in female rats. Together with a greater capacity to produce GSH, these hepatic sex differences might contribute to the sex-different development of diabetes in ZDF rats.

Download Full-text

Faculty Opinions recommendation of Estradiol shifts interactions between the infralimbic cortex and central amygdala to enhance fear extinction memory in female rats.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727002762.793567212 ◽

2019 ◽

Author(s):

Amy Milton

Keyword(s):

Fear Extinction ◽

Female Rats ◽

Infralimbic Cortex ◽

Central Amygdala ◽

Extinction Memory

Download Full-text

The Effects of High Peripubertal Caffeine Exposure on the Adrenal Gland in Immature Male and Female Rats

Nutrients ◽

10.3390/nu11050951 ◽

2019 ◽

Vol 11 (5) ◽

pp. 951 ◽

Cited By ~ 1

Author(s):

Ki-Young Ryu ◽

Jaesook Roh

Keyword(s):

Stress Responses ◽

Adrenal Glands ◽

Tap Water ◽

Female Rats ◽

Male Rats ◽

Water Control ◽

Cortical Function ◽

Male And Female Rats ◽

High Doses ◽

Caffeine Exposure

The consumption of high levels of dietary caffeine has increased in children and adolescents. Human and animal studies have shown that chronic intake of high doses of caffeine affects serum glucocorticoid levels. Given that glucocorticoids play a role in peripubertal organ growth and development, chronic high doses of caffeine during puberty might impair maturation of the adrenal glands. To evaluate any effects of caffeine exposure on growing adrenal glands, 22-day-old male (n = 30) and female Sprague Dawley rats (n = 30) were divided into three groups (n = 10/group); group 1 received tap water (control) and groups 2 and 3 received water containing 120 and 180 mg/kg/day caffeine, respectively, via gavage for 4 weeks. At the end of the experiment, adrenal glands were weighed and processed for histological analysis. Relative adrenal weights increased in both groups of caffeine-fed males and females, whereas absolute weights were decreased in the females. In the female caffeine-fed groups the adrenal cortical areas resembled irregularly arranged cords and the medullary area was significantly increased, whereas no such effects were seen in the male rats. Our results indicate that the harmful effects of caffeine on the adrenal glands of immature rats differ between females and males. Although female rats seemed to be more susceptible to damage based on the changes in the microarchitecture of the adrenal glands, caffeine affected corticosterone production in both female and male rats. In addition, increased basal adrenocorticotropic hormone levels in caffeine-fed groups may reflect decreased cortical function. Therefore, caffeine may induce an endocrine imbalance that disturbs the establishment of the hypothalamo–pituitary adrenal axis during puberty, thereby leading to abnormal stress responses.

Download Full-text

Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats

Neuroendocrinology ◽

10.1159/000496391 ◽

2018 ◽

Vol 108 (4) ◽

pp. 278-290 ◽

Cited By ~ 6

Author(s):

Sanja Kovačević ◽

Jelena Nestorov ◽

Gordana Matić ◽

Ivana Elaković

Keyword(s):

Insulin Resistance ◽

Chronic Stress ◽

Insulin Signaling ◽

Stress Responses ◽

Leptin Receptor ◽

Inflammatory Responses ◽

Receptor Expression ◽

Female Rats ◽

Antioxidative Defense ◽

Appetite Control

Background: Increased fructose consumption and chronic exposure to stress have been associated with the development of obesity and insulin resistance. In the hypothalamus, a crossroad of stress responses and energy balance, insulin and glucocorticoids regulate the expression of orexigenic neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP), and anorexigenic neuropeptides, proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Objectives: We investigated whether chronic stress and fructose diet disrupt these hormonal signaling pathways and appetite control in the hypothalamus, contributing to the development of insulin resistance and obesity. Potential roles of hypothalamic inflammation and oxidative stress in the development of insulin resistance were also analyzed. Methods: Insulin, glucocorticoid, and leptin signaling, expression of orexigenic and anorexigenic neuropeptides, and antioxidative and inflammatory statuses in the whole hypothalamus of fructose-fed female rats exposed to unpredictable stress for 9 weeks were analyzed using quantitative PCR and Western blotting. Results: Chronic stress combined with a fructose-enriched diet reduced protein content and stimulatory phosphorylation of Akt kinase, and elevated 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor expression, while alterations in appetite regulation (NPY, AgRP, POMC, CART, leptin receptor, and SOCS3 expression) were not observed. The expression of antioxidative defense enzymes (mitochondrial manganese superoxide dismutase 2, glutathione reductase, and catalase) and proinflammatory cytokines (IL-1β, IL-6, and TNFα) was reduced. Conclusions: Our results underline the combination of long-term stress exposure and fructose overconsumption as more detrimental for hypothalamic function than for either of the factors separately, as it enhanced glucocorticoid and impaired insulin signaling, antioxidative defense, and inflammatory responses of this homeostasis- regulating center.

Download Full-text

Despite higher glucocorticoid levels and stress responses in female rats, both sexes exhibit similar stress-induced changes in hippocampal neurogenesis

Behavioural Brain Research ◽

10.1016/j.bbr.2012.07.011 ◽

2012 ◽

Vol 234 (2) ◽

pp. 357-364 ◽

Cited By ~ 11

Author(s):

Henriëtte J. Hulshof ◽

Arianna Novati ◽

Paul G.M. Luiten ◽

Johan A. den Boer ◽

Peter Meerlo

Keyword(s):

Stress Responses ◽

Hippocampal Neurogenesis ◽

Female Rats ◽

Induced Changes

Download Full-text

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

International Journal of Molecular Sciences ◽

10.3390/ijms22189847 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9847

Author(s):

Yi-Ju Lee ◽

Hwai-Ting Lin ◽

Muhammad Asad Chaudhary ◽

Yi-Ching Lee ◽

Dean-Chuan Wang

Keyword(s):

Physical Exercise ◽

Stress Responses ◽

Epigenetic Modification ◽

Oxytocin Receptor ◽

Epigenetic Mechanism ◽

Female Rats ◽

Maternal Behaviors ◽

Brain Functions ◽

Pup Retrieval ◽

Dehp Exposure

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