The effect of social isolation and leptin on the hypothalamo-pituitary-adrenocortical (HPA) response to acute stress in rats

The hypothalamo-pituitary-adrenal (HPA) axis is the main regulator of stress in mammals, and prolongation of the stress response can lead to manifestation of metabolic and psychiatric disorders. Leptin is an adipokine known to act at the hypothalamus to regulate body fat stores, appetite and energy expenditure, but the role of leptin on the HPA response to stress is still not well understood. Psychological stress, specifically loneliness in humans - referred to as social isolation (SI) in social mammals - can also alter HPA functioning. The work described in this thesis investigates the effects of leptin and SI on the HPA response to acute stress. My studies suggest that leptin does not influence basal HPA activity, or influence the HPA response to acute endotoxin challenge in rats. They also show that SI does not affect basal HPA activity, but that short term chronic SI does cause hyperactivity of the HPA in response to acute restraint stress, and that the stress axis is hyper-sensitised at the level of the hypothalamus and the adrenal gland after this period of SI. My work suggests that this HPA hyperactivity may be the result of an overactive CRH feed-forward mechanism. I have also shown that short term intermittent SI and long term chronic SI both cause hypoactivity of the HPA axis response to acute restraint stress, with the former regulated by an unknown mechanism and the latter possibly regulated by an overactive glucocorticoid feedback mechanism. In summary, these studies have highlighted the complex differential activation of the HPA axis in response to different types of stressors; both immunological and psychological. I have also demonstrated the different effects of novel SI paradigms on HPA response to acute stress, and how such psychological stress can impair the functioning of a key system in the body that may be involved in metabolic and psychiatric disease.Open Acces

Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic-pituitary-adrenal axis in rats

Copyright @ 2013 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License.Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic-pituitary-adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis.We hypothesised that leptin would attenuate the HPA axis response to sepsis.We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1b secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.The section is funded by grants from the MRC, BBSRC, NIHR and an Integrative Mammalian Biology (IMB) Capacity Building Award, and by a FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. This work is supported by a BBSRC Doctoral Training-Strategic Skills Award grant (BB/F017340/1)

Exploring the synergistic toxicity of synthetic pesticides and their impact on development and behavior of Honeybee (Apis mellifera L.)

In recent years, there has been an increasing concern regarding the impact of pesticide exposure on pollinators, particularly honeybees (Apis mellifera L.). This concern arises from their crucial role in maintaining ecological balance and global food production. Therefore, an extensive investigation has been conducted to explore the intricate relationship between pesticides and the biological development of honey bees in the Rahim Yar Khan region. This study assessed the impact of four pesticides (Emamectin benzoate, Chlorpyrifos, Imidacloprid, and Acetamiprid) on honey bee eggs, larvae, and adult bees under controlled laboratory conditions. The pesticides were applied at concentrations of 10%, 30%, and 50%, as per regional agricultural recommendations. A zero-toxicity control was also included for comparison. Toxicity evaluations were conducted through contact exposure, and Probit and regression analyses were performed using SPSS software to comprehensively assess the toxicity profiles. The study revealed significant adverse effects on the immediate behavioral responses of A. mellifera following pesticide exposure. These effects included heightened agitation, narcotic-like symptoms, audible hovering, crawling, ceased food-sharing behavior, and reduced proboscis extension. Chlorpyrifos exhibited the highest toxicity against adult bees, while Emamectin Benzoate had the least toxicity. Regarding honey bee eggs, Chlorpyrifos, Imidacloprid, and Acetamiprid were notably more toxic, whereas Emamectin Benzoate exhibited the least toxicity. The impact on larvae varied across developmental stages and pesticides, with Imidacloprid, Chlorpyrifos, and Acetamiprid causing significant mortality, while Emamectin Benzoate showed lower toxicity. The study highlights that Emamectin Benzoate demonstrates lower toxicity compared to other insecticides. This emphasizes the importance of balancing effective pest management with the preservation of pollinator health. The findings underscore the need for informed and sustainable approaches to pesticide use, taking into consideration the potential repercussions on honeybee development and behavior