Neural Circuit Mechanism Of Glucose Metabolism Disorder Underlying Stress Condition

The central nervous system combined with the organs and tissues peripheral to control the physiological and metabolic reactions of the living body.The stress response initiated by the central nervous system requires peripheral organs and tissues to provide timely and accurate responses to help animals resist harsh environments and protect their lives;these reactions include autonomic nervous system activity,endocrine system activity,and anxiety.During acute stress response,the central nervous system recruits various nerve nuclei and neural circuits to generate anxiety behaviors to avoid dangerous environments,calls for elevated basal blood glucose to provide energy for stress response,and regulates the release of stress hormones to maintain stress reaction.Underlying long-term stress circumstances,behavior,physiology,and metabolism are disrupted,animal suffering from anxiety,type 2 diabetes,and osteoporosis.In this study,we explored the changes in basal blood glucose and basal metabolism after stress stimulation;the central nervous system mechanism of stress-induced anxiety responses;the central nervous system mechanism of stress-induced basal blood glucose changes;the nervous system mechanism of stress-induced osteoporosis.Stress disrupts fluctuations in basic blood glucose in rodentsBasic blood glucose is an important indicator for assessing blood glucose metabolism and diagnosing diabetes.Under physiological conditions,the basic blood sugar is affected by daily activities and external stimuli,is in a dynamic balance,and maintains a circadian rhythm.Stress can lead to elevated blood sugar,but how stress affects fluctuations in basal blood glucose is unclear.By continuously monitoring the basal blood glucose of mice under physiological conditions,we found that blood collection operations and light body weight caused an increase in basal blood glucose fluctuations in mice.Continuous monitoring of basal blood glucose levels for 24 hours,we found that basal blood glucose strictly follows the circadian rhythm;when given stress stimulation,the basal blood glucose circadian rhythm is impaired;after three days of stress stimulation,the circadian rhythm of basal blood glucose is still not restore.It is proved that acute stress leads to an increase in irregular fluctuations in basal blood glucose in mice,and relatively long-term stress causes an irreversible change in the circadian rhythm of basal blood glucose in mice.The results of this study provide a new perspective for the mechanism of blood glucose disorders caused by stress stimulation,and provide possible indicators for clinical diagnosis of glucose metabolism disorders and type 2 diabetes.The GABAergic neural circuit from the aBNST to the ARC mediates stress responseStress stimulation elicits anxiety and endocrinal function changes.A set of overlapping neurocircuits mediate the behavioral and endocrinal components of the stress responses.Previous studies have shown that the aBNST is involved in stress response;however,How the GABAergic neurons and the calcium-dependent protein kinase II(CaMKII)-labeled neurons and neural circuits in the aBNST to participate the stress regulation has not been clearly explained.In this study,we used optogenetic technique to manipulate the GABAergic neurons and CaMKII neurons in the aBNST to study anxiety-like behavior and stress hormones in mice.We found that the activation of GABAergic projecting from the aBNST to the ARC mediates anxietylike behavior,and elevated levels of stress hormones such as corticosterone and adrenaline.Optogenetics inhibits the GABAergic projecting from the aBNST to the ARC produced anxiolytic behavior in mice and reversing the increasing of the corticosterone and norepinephrine due to restraint stress.Pharmacogenetics inhibits the GABAergic pathway from the arcuate nucleus(ARC)to the solitary tract nucleus(NTS)and then,activates the GABAergic projecting from the aBNST to the ARC by optogenetics,mice show no anxiety-like behavior.The results of this study suggest that the GABAergic pathway from the ARC to the NTS mediates the transfer of anxiety-like behavior information,produced by activation of the GABAergic projecting from the aBNST to the ARC.This study lays the foundation for further elucidating the sub-type neurons mechanism of anxiety behavior in stress response and provides a potential therapeutic target for the treatment of anxiety caused by stress anxiety.GABAergic neural circuit mediated stress response mediated hyperglycemiaHow does stress call for increasing of basal blood sugar called? In this study,we used optogenetic to manipulate GABAergic and CaMKII neurons in the aBNST.We found that activation of GABAergic neurons of the aBNST lead to hyperglycemia,while CaMKII inhibition or activation do not changes the blood glucose,and activation of glutamatergic neurons in the aBNST does not affect acute glycemic.Activation of the glutamatergic neural pathway from the aBNST to the VMH failed to directly change the basal blood glucose,but induced a delayed hyperglycemia.However,activation of the GABAergic neural circuits from aBNST to the ARC causes acute hyperglycemia;After removal of the adrenal gland,activation of the GABAergic pathway from the aBNST to the ARC still elicits hyperglycemia;After pharmacogenetics specifically inhibits the GABAergic projection from the ARC to the Raphe Obscurus(ROb),the activation of the GABAergic pathway from the aBNST to the ARC causes a rapid decline in basal blood glucose levels.This result reveals a GABAergic pathway of the aBNST-ARC mediates calling for blood glucose to provide energy for the stress response.This study lays the foundation for further study of the regulation of islet function by the neural circuit and provides an important target nucleus for the treatment of blood glucose disorders caused by stress.Stress affects bone metabolism by activating the sympathetic nervous systemLong-term excessive stress leads to metabolic disorders,such as obesity,weight loss,and osteoporosis.In this study,we explored the neural mechanisms underlying stress-induced osteoporosis.We tested the changes in the amount of tibia bone after long-term stress stimulation in mice.It was found that the average bone mass of the mice was significantly lower as compared with the control group.Pharmacogenetics inhibits somatostatin-labeled neurons in the aBNST reverse bone loss caused by stress;In further exploration,the norepinephrine secreted by the sympathetic nervous system inhibits differentiation of bone marrow mesenchymal stem cells into osteoblast.This study found a possible therapeutic target for bone loss caused by stress,and laid the foundation for further exploration of central nervous system to regulate bone metabolism.