In recent years, more and more studies have confirmed that negative emotions such as anxiety and depression caused by chronic stress can lead to metabolic imbalances, resulting in people “not eating well” and “sleeping well” , however, its underlying neural mechanism is unclear.
Beijing time on March 22, in a new study published in Molecular Psychiatry, from the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (Shenzhen Institute of Advanced Technology) Researcher Yang Fan‘s research group found that under chronic stress stress, the cluster firing of neurons in the ventromedial nucleus of the hypothalamus (VMH) in the brain is involved in Anxiety and regulation of energy metabolism. This study not only deeply analyzes the neural mechanism of stress-induced anxiety and metabolic abnormalities, but also provides new intervention strategies for intervening anxiety and other related diseases.
Stress-induced anxiety is a common emotional state, but chronic anxiety not only affects mental health, but also has serious negative effects on the body’s physiological functions. A lot of evidence shows that when you are in a state of excessive anxiety and stress for a long time, the sympathetic nerves of the body will be overexcited and lead to physiological homeostasis such as abnormal glucose and lipid metabolism, endocrine disorders, and bone loss. However, stress affects anxiety and metabolism. The neural mechanism is still not fully understood. In addition, a series of studies in recent years have also found that VMH can play an important role in the regulation of anxiety and metabolism, but the neural mechanism of its neurons regulating anxiety and energy metabolism under stress also needs to be further analyzed.
Through research, the team first discovered that chronic stress-stressed mice developed anxiety-like behaviors and abnormal metabolic balance (reduced food intake, decreased energy expenditure), and clustered firing neurons in the VMH nuclei The proportion and intensity of , will also increase significantly. Modulation of VMH neurons using optogenetic techniques can induce cluster firing and enhanced VMH calcium activity; persistently evoked cluster firing can mimic chronic stress-like anxiety-like behaviors and metabolic changes.
In order to further verify the mechanism of cluster discharge, the research team used a series of techniques such as in vitro electrophysiology, in vivo drug delivery, and RNAi interference to find that calcium ion channel Cav3.1 can mediate VMH. Neuronal cluster firing; and, decreased Cav3.1 expression significantly reduced the proportion of cluster-firing neurons in the VMH of anxious mice, thereby alleviating anxiety-like behavior and metabolic abnormalities in mice. In addition, the anti-anxiety drug, fluoxetine, taken for a long time in chronic stress-stressed mice can reduce the proportion of cluster-firing neurons, block chronic stress-induced anxiety and alleviate abnormal peripheral energy metabolism. In conclusion, this study revealed the important role of VMH nuclei neuron cluster firing in regulating chronic stress-induced anxiety-like behaviors and metabolic changes, and also suggested that calcium channel Cav3. Potential targets for intervention in anxiety stress disorders.
VMH neuron cluster firing regulates anxiety-like behavior and energy metabolism
Yang Fan’s research team has been conducting research on the mechanism of central nervous system regulation of bone metabolism for a long time. Earlier, Yang Fan’s team and collaborators found that VMH is involved in the neural circuit of chronic stress-induced anxiety and bone loss (Journal of Clinical Investigation. 2020), light regulation of parathyroid hormone secretion to interfere with bone loss (Nature Communications. 2022); the latest research is another important achievement of the team’s continued in-depth exploration of the field of “central nervous system regulation of peripheral metabolism” based on the previous foundation.
This research project received valuable advice and assistance from Researcher Wang Liping of Shenzhen Advanced Institute and Professor Hu Hailan of Zhejiang University, and was supported by the National Natural Science Foundation of China, the Chinese Academy of Sciences, Guangdong Province and Shenzhen City.