Effects of Chronic Restraint Stress on Body Weight, Food Intake, and Hypothalamic Gene Expressions in Mice

Jeong, Joo; Lee, Dong Hoon; Kang, Sang Soo

doi:10.3803/enm.2013.28.4.288

Cited by 165 publications

(119 citation statements)

References 33 publications

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“…These data prompted us to test the effect of stress on pup interactions and PeFA Ucn3 neuronal activity. Confirming previous reports 24,25 , chronic restraint stress in virgin females led to weight loss, reduced pup retrieval, and a decreased fraction of parental females ( Fig. 3g-i).…”

Section: Pefa Ucn3 Neurons Receive Input From Parenting and Stress-assupporting

confidence: 92%

Urocortin-3 Neurons in the Mouse Perifornical Area Promote Infant-directed Neglect and Aggression

Autry

Zheng

Kapoor

et al. 2019

Preprint

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Mammals invest considerable resources in protecting and nurturing young offspring. However, under certain physiological and environmental conditions, animals neglect or attack young conspecifics. Males in some species attack unfamiliar infants to gain reproductive advantage [1][2][3] and females kill or neglect their young during stressful circumstances such as food shortage or threat of predation 4-8 . In humans, stress is a risk factor in both sexes for peripartum disorders and associated impairments in parent-infant interactions 9 . While recent studies have uncovered dedicated neural pathways mediating the positive control of parenting 10-13 , the regulation of infantdirected neglect and aggression and the relationship between these behaviours and stress are poorly understood. Here we show that urocortin-3 (Ucn3)-expressing neurons in the perifornical area (PeFA Ucn3 ) of the hypothalamus are activated during infant-directed attacks in males and females, but not other forms of aggression. Opto-and chemogenetic manipulations of PeFA Ucn3 neurons demonstrate the role of this neuronal population in the negative control of parenting in both males and females. PeFA Ucn3 neurons receive input from areas associated with vomeronasal sensing, stress, and parenting, and send major projections to the ventromedial hypothalamus (VMH), ventral lateral septum (LSv) and amygdalohippocampal area (AHi). Optogenetic activation of PeFA Ucn3 axon terminals in these regions triggers different aspects of infant-directed agonistic responses, such as neglect and aggression. Thus, PeFA Ucn3 neurons emerge as a critical hub for the expression of infant-directed neglect and aggression, providing a new framework to examine the positive and negative regulation of parenting. RESULTS Urocortin-3 expressing cells in the perifornical area are specifically activated during infant-directed aggressionTo identify brain areas involved in infant-directed aggression, we monitored the induction of the immediate early gene (IEG) c-fos across the hypothalamus and septal and amygdaloid nuclei in 3 infanticidal virgin males, fathers, and mothers after interactions with pups ( Fig. 1a-b).Significantly more c-fos positive cells were found in the medial bed nucleus of stria terminalis (BNSTm), the LSv, and PeFA of infanticidal males compared to mothers and fathers, with the most robust differences observed in the PeFA, a small nucleus between the fornix and the paraventricular hypothalamus (PVH) (Fig. 1a, b). By contrast, fewer c-fos positive cells were observed in the medial preoptic area (MPOA) of infanticidal males compared to mothers, as expected from previous studies 13,14 (Fig. 1a, b). To identify markers of PeFA cells activated by infant-directed attacks, we visualized c-fos expression in tissue sections from virgin males after interactions with pups and performed microdissections of the corresponding areas in adjacent sections followed by gene expression analysis of the micro-dissected material (Fig. 1c).Expression analysis (see Methods) revealed 26...

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Section: Pefa Ucn3 Neurons Receive Input From Parenting and Stress-assupporting

confidence: 92%

Urocortin-3 Neurons in the Mouse Perifornical Area Promote Infant-directed Neglect and Aggression

Autry

Zheng

Kapoor

et al. 2019

Preprint

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“…It seems that the direction and intensity of NPY expression is largely dependent on the stress type and duration. While stimulatory effects of acute [37] and inhibitory effects of chronic stress [38] have been generally reported, some studies [39, 40], including the one presented herein, indicate that stress does not affect the expression of orexigenic neuropeptides even though it reduces body weight. Considering this, glucocorticoid hormones, as mediators of stress responses, do not necessarily affect appetite to change fat mass.…”

Section: Discussionmentioning

confidence: 97%

“…Plasma leptin is directly proportional to adipose tissue mass [13], and our results reflect this correlation since stressed animals have been reported to have significantly reduced visceral adipose tissue mass [35] and plasma leptin regardless of the diet. The ability of stress to reduce plasma leptin level without increasing appetite was previously demonstrated [40]. Even a stress-induced increase in leptin and leptin receptor levels does not necessarily affect NPY expression [41].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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.

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“…Agomelatine antagonizes serotonin 2C receptor which is an important mediator of satiety [15]. It is well established from studies conducted earlier that restraint stress model in mice induces depression such as state in addition to the reduction in body weight and food intake by altered expression of food related genes like decreased ghrelin and increased Pro-opiomelanocortin [16,17].…”

Section: Discussionmentioning

confidence: 99%

A Study on the Effects of Agomelatine on Food Intake and Body Weight in Restraint Stress Model in Adult Swiss Albino Mice

Priya

Nivedhithaa

Huvaneswari

2017

Asian J Pharm Clin Res

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Objectives: Agomelatine is a novel melatonin (MT) receptor agonist at MT 1 and 2, serotonin receptor antagonist and an effective chronobiotic agent. The study was designed to evaluate the effects of agomelatine on body weight and food intake in restraint stress model in adult Swiss albino mice. Methods:After the approval of Institutional Animal Ethics Committee, 40 male Swiss albino mice were randomly divided into four groups of 10 animals each; two were treatment groups which received 25 mg/kg (low dose) agomelatine, 50 mg/kg (high dose) agomelatine, standard group given trazodone and the control group administered the vehicle (1% hydroxyethyl cellulose [HEC]) intraperitoneally for the last 14 days in the 3 weeks study period. Chronic restraint stress was given for 4 hrs per day for all groups starting from day 0 to 21. Results:Using paired t-test, both 12 hrs (p=0.011) and 24 hrs (p<0.001) food intake in the high dose agomelatine group were significantly increased. Between groups using ANOVA test showed a statistically significant increase in food intake for this group when compared to the control group. Unlike the low dose agomelatine group (p=0.205), the mean body weight in the group treated with high dose agomelatine revealed a statistically significant rise compared to that of the control (p=0.001) in ANOVA test. Conclusion:High dose agomelatine was effective in antagonizing the body weight lowering effect of restraint stress in addition to amelioration of reduced food intake. The study has potentially brought out the additional therapeutic benefit of agomelatine in improving the altered feeding and body weight changes when used in the treatment of the depression.

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Effects of Chronic Restraint Stress on Body Weight, Food Intake, and Hypothalamic Gene Expressions in Mice

Cited by 165 publications

References 33 publications

Urocortin-3 Neurons in the Mouse Perifornical Area Promote Infant-directed Neglect and Aggression

Urocortin-3 Neurons in the Mouse Perifornical Area Promote Infant-directed Neglect and Aggression

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

A Study on the Effects of Agomelatine on Food Intake and Body Weight in Restraint Stress Model in Adult Swiss Albino Mice

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