Astrocytes Play Hidden Role in PTSD Development and Treatment

Recent research has uncovered a surprising contributor to post-traumatic stress disorder (PTSD), highlighting the active role of astrocytes—star-shaped support cells in the brain—in the persistence of traumatic memories. Patients with PTSD often find it difficult to forget distressing memories, even long after the traumatic event has passed, posing a significant challenge for effective treatment.

A study conducted by scientists at the Institute for Basic Science (IBS) and Ewha Womans University has identified a novel brain mechanism that drives PTSD symptoms. Published in Signal Transduction and Targeted Therapy, the research reveals that astrocytes in the brain produce excessive gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter. This overproduction impairs the brain’s capacity to extinguish fear memories, especially in the medial prefrontal cortex (mPFC), a brain region essential for fear regulation.

The study involved brain imaging of more than 380 participants and postmortem analysis, which showed elevated GABA levels in PTSD patients, along with reduced blood flow in the mPFC. Notably, patients who improved clinically showed decreased GABA levels, indicating a crucial role of this neurotransmitter in recovery.

To understand the cellular origins of excessive GABA, researchers studied PTSD-like mouse models and human brain tissue. They discovered that astrocytes, rather than neurons, are responsible for the abnormal GABA production. This production is mediated by the enzyme monoamine oxidase B (MAOB). The abnormal GABA impairs neural activity and prevents the brain from effectively forgetting traumatic memories.

Encouragingly, the team tested a drug named KDS2010, a highly selective and reversible MAOB inhibitor, which can cross the blood-brain barrier. When administered to the mice, KDS2010 normalized GABA levels, increased blood flow in the mPFC, and restored fear extinction mechanisms. Since KDS2010 has already completed Phase I safety trials in humans, it presents a promising candidate for future PTSD therapies.

Current treatments for PTSD, primarily targeting serotonin pathways, provide limited relief for many patients. The new findings focus on the medial prefrontal cortex’s role in fear regulation and suggest that decreasing astrocytic GABA production could be a more effective approach. The research exemplifies a 'reverse translational' strategy, linking clinical brain scans to cellular mechanisms and confirming these findings in animal models.

Lead researcher Dr. C. Justin Lee emphasized that these findings highlight the active role of glial cells—formerly considered passive support cells—in psychiatric disorders. The identification of astrocytic MAOB as a key driver opens new avenues for treating PTSD and potentially other neuropsychiatric conditions, such as depression, schizophrenia, and panic disorders.

With KDS2010 progressing through clinical trials, this discovery sets the stage for innovative treatments that target the cellular mechanisms underlying traumatic memory retention, offering hope for patients unresponsive to conventional therapies.

Source: https://medicalxpress.com/news/2025-07-astrocytes-hidden-culprit-ptsd.html