Anxiety is one of the common mental illness.According to a large -scale population survey, up to 33.7%of people suffer from anxiety in their lives.Inflammation is one of the important mechanisms of stress anxiety. Cytosaceous intervention or anti -inflammatory drug treatment can improve the anxiety behavior of rodents. Small gum cell is the main immune cells in the brain, which plays a core role in neuritis, immune surveillance and maintaining the stability of the brain.Therefore, anti -inflammatory treatment for small glue cells may be one of the effective strategies for clinical treatment of anxiety.
On February 22, 2024, the Team of Pharmacology at the Medical College of Southern University of Science and Technology published in the IMMUNITY journal entitled: Disruption of Na +/K + -TPase-P2X7R Complex in the Microglia Promotes Stress-INDuced Anxiety.
reveals the new function of Na+/K+-ATP enzyme (also known as sodium potassium pump, NKA) anti-inflammatory function, and uses this to propose NKAAntibody therapy, the study also found that NKA on a stable small glue film is likely to become a new strategy for treating stress anxiety.
NKA by trapped three NA + cells and two K + into cells, maintaining the electrochemical gradient on the cell membranePlay an important role.NKA also participates in the CA 2+ signal transformation and neurotransmitting release by coordinating the gradient gradient on the cell membrane.At the same time, NKA can also cooperate with multiple ion channels on the cell membrane to form a dynamic network of ion steady -state regulation, and affect cell communication by regulating chemical signals and ion balance between different types of cells.However, NKA is not only a simple ion pump, but also a signal transmission protein or cell protective protein.
卞 劲 松 Professor group has been paying attention to NKA physiological functions and its role in the occurrence of diseases for a long time.In 2021, Jinsongs research team published a paper published in the Science Advances journal. For the first time, the loss of NKAs NKA in the dopamine neuron is an important mechanism of Parkinsons disease.The paper published this time in Immunity , once again discovered the important role of NKA on the occurrence of anxiety in small glue cells.
Through a variety of behavioral experiments such as the absence of the field and the cross -elevated maze, the researchers found that NKAα1s whole body knocked low mice in the restraint should be stimulated and the sole electric shock model was obvious.serious.Injecting AAV viruses to generate abdominal hippocampus (VHIP) NKAα1 specific knocking mice with low -cut mice and low -collapse cell NKAα1 specific knockout mice through the brain area and knockout miceObviously aggravated.To further detect neuritis in VHIP through biochemical experiments, it is found that the further activation of small gel cells has led to the super excitement of neurons, which leads to an increase in anxiety epitoma.These results indicate that NKAα1 on small glue cells in VHIP has an important impact.
In order to explore the mechanism of NKAα1 to media neuritis, through in -situ hybrid experiments, immune co -precipitation technology, and primary neurons, star gum cells, small glueQuality cells, researchers have found that NKAα1 and a purine energy receptor P2X7R have interaction.With surface plasma resonance technology (SPR), the researchers confirmed the existence of NKAα1-P2X7R complex.Through this complex, NKAα1 effectively reduced the K + row of P2X7R mediated, resisting the activation of small gel cells.However, in stress state, the loss of NKAα1 in the membrane of the cell membrane has promoted the K+discharge of the free state P2X7R mediated, and aggravated the release of the inflammatory factor IL-1β.
Based on the above pathological mechanism, researchers have developed a monoclonal antibody targeting NKA α1 outer segments. This antibody can stabilize the expression of NKAα1 on the cell membrane.This prevents the occurrence of neuritis, reduces the excitement of VHIP neuron, and achieves the role of the treatment of mice.
This research not only reveals the function of coordinating neurons in a healthy and pathological state, but also the treatment of anxietyIt provides a potential new target, and it also provides valuable new directions for clinical diagnosis and treatment of stressful mental illness.
PhD students Huang Songqiang of the School of Medicine, Southern University of Science and Technology, as the first author of the paper, Shenzhen Peoples Medical College Nie Xiaowei associate researcher and Nan NanProfessor 卞 劲 松 , director of the Department of Pharmacology of HKUST Medical College, is the author of the paper.Lin Xiaoqian, a masters degree in the University of Science and Technology of China, Xu Kang Tai, a doctoral graduate student, and undergraduate Li Kun also participated in the study.
Thesis link :
https://doi.org/10.1016/j.immmuni.2024.01.018
