Electroacupuncture decreases microglia-mediated synaptic engulfment to ameliorate CUMS-induced depressive-like behaviors in the mPFC.

Feeling depressed can be overwhelming, and many people are searching for treatments that go beyond standard medications. A new study published in the Journal of Affective Disorders offers encouraging news about electroacupuncture — a form of acupuncture that uses gentle electrical stimulation through the needles — and how it may help the brain recover from depression at a cellular level.

Researchers used a well-established animal model called Chronic Unpredictable Mild Stress (CUMS) to simulate depression in mice. After three weeks of stress exposure, the mice received three weeks of electroacupuncture at two familiar acupuncture points: Baihui (GV20), located at the top of the head, and Yintang (GV29), positioned between the eyebrows. These points are commonly used in clinical practice for mood and mental health support.

What the scientists discovered was remarkable. Depression appears to involve overactive brain immune cells called microglia, which begin mistakenly "eating" healthy synapses — the vital connections between brain cells — in the prefrontal cortex, the area of the brain responsible for decision-making, emotion, and behavior. This excessive synaptic pruning leads to a loss of brain connectivity associated with depressive symptoms.

Electroacupuncture treatment significantly reversed these changes. It calmed the overactive microglia, protected synaptic connections, and improved both depressive and anxiety-like behaviors in the mice. The researchers identified a specific molecular pathway — called TREM2/DAP12 — as the key mechanism through which electroacupuncture achieves these effects. When this pathway was blocked in genetically modified mice, electroacupuncture lost its protective benefits, confirming its importance.

This research suggests that electroacupuncture may help restore healthy brain function by protecting neural connections from immune-driven damage — a meaningful finding for anyone exploring holistic approaches to depression care. If you are considering electroacupuncture, seek treatment from a licensed, qualified acupuncturist experienced in mental health conditions.

This preclinical study (Journal of Affective Disorders) investigated the neurobiological mechanisms underlying electroacupuncture's (EA) antidepressant effects in a CUMS mouse model. EA was administered at GV20/GV29 for three weeks post-stress induction. Behavioral assessments (FST, SPT, TST, OFT, EPM) confirmed significant amelioration of depressive- and anxiety-like phenotypes following EA treatment. Mechanistically, EA suppressed aberrant microglial phagocytosis of synapses in the medial prefrontal cortex (mPFC), preserving synaptic density as confirmed via immunofluorescence and Golgi staining. The TREM2/DAP12 signaling pathway was identified as the critical mediator: EA upregulated TREM2/DAP12 expression, and genetic knockout of TREM2 abolished EA's protective effects on microglial activation, synaptic integrity, and behavioral outcomes. These findings provide a mechanistic framework linking EA stimulation to microglial homeostasis and synaptic preservation in the mPFC. Clinically, this supports EA's potential as a neuroinflammatory-targeted intervention in depression management, particularly for patients with treatment-resistant presentations.