Common mood disorders are not only affected by psychological factors, but also have a corresponding neurobiological basis. Recently, Professor Chen Jianguo from the Tongji Medical College of Huazhong University of Science and Technology has made new progress in the pathogenesis of anxiety disorders and drug therapy research. The series of research results have recently been published online in the leading journal Psychiatry, Biological Psychiatry.
The team found that autophagy regulates the new role of fear memory. Autophagy is a self-eating phenomenon in cells, which is a defense and stress regulation mechanism of the body. Professor Chen Jianguo's team found that fear stimulation stimulates the formation of autophagic vacuoles involved in the GABAA receptor transporter GABARAP in the amygdala brain region of mice, causing a decrease in GABAA receptor endocytosis and membrane expression. Administration of the autophagy inhibitor SAR405 attenuates the consolidation of fear memory by blocking GABARAP-mediated autophagy formation. This result not only reveals the clinical potential new use of autophagy inhibitor SAR405, but also suggests that GABARAP is expected to become a new target for the treatment of anxiety.
The team revealed a new mechanism by which diazepam regulates GABA receptors. As a commonly used anti-anxiety drug in the clinic, diazepam acts by promoting the opening of the chloride channel by acting on the GABAA receptor. Professor Chen Jianguo's team research found a new mechanism of action. Diazepam can increase the membrane stability of the GABAA receptor by promoting palmitoylation of the GABAA receptor anchoring protein Gephyrin in the mouse amygdala brain region, thereby producing an anxiolytic-like effect. This study suggests that regulation of Gephyrin and its palmitoylation modification is expected to be a new target for the treatment of anxiety.
The above series of research work was funded by the National Natural Science Foundation's Innovation Research Group, the 973 Program, and the Ministry of Education's “Innovation Team Development Programâ€.
Source: Ministry of Science and Technology
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