Studies On The Response And Regulatory Function Of Hypothalamus Araventricular Nucleus To Pathogenic Systemic Inflammation

The endotoxin lipopolysaccharide(LPS)is the active component of the cell wall of Gram-negative bacteria,when injected into animals,resulted in the production of proinflammatory cytokines which will cause systemic inflammation initiate and a specific set of pathophysiological and behavioral changes.however,the role of these changes in host defense is largely unknown.Interactions between the immune and neuroendocrine systems is necessary for organisms to overcome pathological events such as inflammation or infection.The hypothalamic paraventricular nucleus(PVN)is an important nucleus that responds to homeostatic changes by integrating neuroendocrine,autonomic and behavioral responses such as infection.Hypothalamic paraventricular nucleus with nerve impulses to obtain a large amount of information,when feeling the need,it will release all kinds of chemicals to the pituitary gland,which regulates the balance of the body's homeostasis.The main purpose of this project is using neurobiological techniques to specific manipulation of the hypothalamic paraventricular nucleus,by analyzing the cytokines,neurotransmitters,neuropeptides and endocrine hormones to preliminary explore the role of the hypothalamus paraventricular nucleus in neuroendocrine-immune system;Meanwhile,by analyzing the animal behavior in the inflammatory model to explore the role of the hypothalamic paraventricular nucleus in host defense.It will provide some new theoretical basis for further research on how the nervous system regulates the organism when the pathogens invade.The research content of this project is mainly divided into the following contents: 1.The effect of systemic inflammation on homeostasis and behavior induced by LPSIntraperitoneal injection of LPS can lead to the rise of the central and peripheral cytokines and activation of the HPA axis,causing immune activation.Hypothalamus and pituitary gland constitute a complete neuroendocrine function system,which is also be affected by LPS.To explore the effects of systemic inflammation induced by LPS on the homeostasis and behavior of mice,we first analyzed the gene expression profile of anterior pituitary cells.After LPS injection one hours,specific hormones,neuropeptides and their corresponding signal pathways are changed,meanwhile many cytokines are produced,leading to the change of body homeostasis.Next,we conducted a series of measurements of animal behavior.Within 24 hours after LPS injection,mice showed a series of disease behavior characteristics,such as decreased on food and water intake,exercise ability,oxygen consumption and body temperature.2.The regulation of hypothalamus paraventricular nucleus on the homeostasis under the systemic inflammation induced by LPSThrough immunofluorescence staining and fiber optic calcium signal detection,we find that PVN has significant neural activity on LPS stimulation.Meanwhile,PVN plays an important role in regulating energy balance and neuroendocrine homeostasis.To investigate how PVN affects and regulates homeostasis under LPS stimulation,we inhibited PVN.Through analysis,we found some important hormones,receptors,neuropeptides and some important signaling pathways,which are crucial for the regulation of PVN under the inflammation.3.The effect of hypothalamus paraventricular nucleus on the behavior under the systemic inflammation induced by LPSAn important function of the central nervous system is to regulate animal behavior in response to changes.Previous results have shown that LPS injections can cause weight loss and hypothermia.To understand the mechanism behind this regulation of the nervous system,we used virus tracer technology to describe the whole brain input network of PVN.The analysis revealed a link between PVN and many brain regions,including lateral hypothalamic nucleus,the "hunger center" that controls feeding,and preoptic area,the thermoregulatory center.For this reason,we have the necessity to research the circuits that cause weight loss and hypothermia.The results showed that the body temperature and weight of mice could be recovered quickly by a series of regulation of PVN in response to the stimulation of pathogens invasion.Therefore,PVN plays a particularly critical role in response to pathogens stimulation.4.Activation of hypothalamus paraventricular nucleus can alleviate the diseaseThrough the activation of the hypothalamus paraventricular nucleus,we found that the recovery time of weight loss and hypothermia caused by LPS was significantly shortened,it is indicated that the hormones and cytokines released by the hypothalamus paraventricular nucleus played an important role in the recovery of disease behaviors.In this study,virus tracer technique is used to describe the whole brain input network of the hypothalamus paraventricular nucleus,which helps us to better understand the role in integrating sensory information,transmitting and regulating endocrine activities and physiological functions.Through the application of chemical genetics technology to manipulate the hypothalamus paraventricular nucleus,revealing the hypothalamus paraventricular nucleus plays an important regulatory role in the fight against LPS stimulation and supplement the understanding of the function of the hypothalamus paraventricular nucleus in the fight against diseases.