New Therapeutic Substance Discovered for Depression and Post-Traumatic Stress Disorder

DGIST Professors Ko Jaewon and Eom Jiwon Research Team Discovers New Candidate Substance for Anxiety Disorder Correction

[Asia Economy Reporter Kim Bong-su] A new substance capable of treating depression and post-traumatic stress disorder (PTSD) has been discovered.

The Daegu Gyeongbuk Institute of Science and Technology (DGIST) announced on the 21st that a joint research team led by Professors Jae-Won Ko and Ji-Won Eom from the Department of Brain and Cognitive Sciences discovered a new candidate target that can correct anxiety disorders by regulating inhibitory synaptic neurotransmission within brain neural circuits. DGIST explained, "This is expected to present a new research direction for developing novel treatments for brain psychiatric disorders accompanied by anxiety disorders, such as depression and PTSD."

Synapses function as special gateways that transmit neural information quickly and accurately, governing all brain functions. Synapses are divided into excitatory and inhibitory types, which act antagonistically to maintain the balance of neural circuit networks, ensuring normal brain function. In particular, when inhibitory synapses in specific regions are damaged, memory loss, autism, and depression can occur, but there has been no established molecular principle explaining how these mechanisms are regulated.

In this context, the research team first identified the inhibitory synapse protein IQSEC3 in 2016. Last year, they revealed that IQSEC3 is a key factor regulating inhibitory synapse development by controlling neural circuit activity and the amount of somatostatin peptide in the hippocampal dentate gyrus, a brain region mediating higher functions such as memory and learning.

In the current study, it was demonstrated that the IQSEC3 protein acts as a downstream factor of the core transcription factor Npas4, which mediates inhibitory synapse development in response to external stimuli, regulating synaptic neurotransmission of specific inhibitory neurons that secrete somatostatin within the hippocampus. Using chemogenetics techniques, the researchers confirmed that the pathway involving the upstream factor Npas4 and downstream IQSEC3 controls the activity of inhibitory neurons in the brain, thereby regulating anxiety behaviors. Notably, the IQSEC3 protein promotes the secretion of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits neuronal activity, proposing a novel mechanism that controls specific behaviors through regulating network activity within the hippocampus.

Professor Ko stated, "We have consistently secured evidence that IQSEC3 protein regulates the activity of brain inhibitory neural circuits," adding, "By elucidating a new rule where IQSEC3 functions as a key factor maintaining excitatory-inhibitory balance, it may help in developing treatments for brain psychiatric disorders such as anxiety disorders."

The research findings were published online on the 20th in the international journal Cell Reports.