Electroacupuncture Eases Cognitive Impairment in Schizophrenia Model Mice

Electroacupuncture at the Zusanli (ST36) acupoint improved cognitive performance in a mouse model of schizophrenia-associated cognitive impairment, according to a preclinical study published in Behavioral and Brain Functions. The research, using mice treated sub-chronically with the NMDA receptor antagonist MK-801, reported a time-dependent pattern of behavioral recovery alongside reductions in neuroinflammation, modulation of BDNF-TrkB signaling, and partial shifts in neural communication between two brain regions central to cognition.

The behavioral results unfolded progressively over three weeks of treatment. In the first week, electroacupuncture elevated the novel object recognition index, a measure of recognition memory. By the second week, it enhanced performance in the novel location recognition task, which probes spatial memory.

To probe the mechanisms behind these gains, the researchers examined cellular activity in the hippocampus and medial prefrontal cortex, two interconnected regions critical for memory and executive function. Electroacupuncture increased the expression of c-Fos, a marker of neuronal activation, in both areas of the model mice, indicating heightened engagement of these circuits during cognitive processing.

A second line of evidence pointed to suppressed neuroinflammation. The treatment reduced microglial overactivation, the exaggerated immune response of the brain’s resident immune cells that is increasingly implicated in neuropsychiatric disease. Levels of pro-inflammatory cytokines, including IL-1β, IL-6, IL-17A, and TNF-α, were lowered in both the hippocampus and the medial prefrontal cortex, consistent with a calming of the inflammatory environment that can disrupt synaptic function.

The study also documented changes at the synaptic level. Electroacupuncture upregulated postsynaptic density protein 95 (PSD-95) and synaptophysin (SYP), two proteins essential to the structure and function of synapses. It modulated the brain-derived neurotrophic factor–tyrosine kinase B (BDNF-TrkB) signaling pathway, a key regulator of synaptic plasticity, and rescued the loss of dendritic spine density and morphological complexity, structural features that support communication between neurons. Together, these changes may underlie the improved synaptic plasticity observed in treated animals.

Electrophysiological recordings added a circuit-level dimension to the findings. In vivo extracellular recordings during cognitive tasks revealed trending elevations in oscillatory activity in the ventral hippocampus and in theta–gamma phase-amplitude coupling between the ventral hippocampus and the medial prefrontal cortex after treatment. The authors are careful to note, however, that these electrophysiological shifts did not reach statistical significance, marking them as suggestive rather than conclusive evidence of reorganized functional connectivity.

Taken together, the multi-level findings suggest that the cognitive improvements in the model mice correlate with reduced neuroinflammation, adjusted BDNF-TrkB-associated synaptic plasticity, and partial shifts in ventral hippocampus–medial prefrontal cortex functional connectivity. The study frames electroacupuncture as a potential non-pharmacological approach to schizophrenia-associated cognitive impairment, a symptom the authors describe as core, treatment-resistant, and severely compromising to patients’ functional outcomes and quality of life.

Important caveats frame the work. The evidence comes from a sub-chronic MK-801 mouse model, an animal paradigm rather than human patients, and the authors emphasize that robust clinical evidence confirming electroacupuncture’s efficacy for this condition remains limited. They explicitly state that rigorous clinical trials are still required to confirm its translational efficacy and clinical application value. The electrophysiological results, being statistically non-significant, should be interpreted as preliminary. Even so, the convergence of behavioral, inflammatory, synaptic, and circuit-level observations offers a coherent preclinical picture of how a targeted acupuncture intervention might act on the biology of cognitive impairment, and a benchmark for what future human studies will need to test.

Subject of Research: Preclinical effects of electroacupuncture on cognitive impairment, neuroinflammation and synaptic plasticity in an MK-801 mouse model of schizophrenia-associated cognitive impairment

Article Title: Electroacupuncture alleviates cognitive impairment through neuroinflammation suppression, BDNF-TrkB pathway modulation and vHIP-mPFC neural oscillation reorganization in sub-chronic MK-801 treated mice

Article References: Xie, Y., Zhou, M., Tang, W., Wang, Q., Li, Y., Tian, J., Feng, J., Wang, Z., Gao, F., Gu, J., & Wang, Z. (2026). Electroacupuncture alleviates cognitive impairment through neuroinflammation suppression, BDNF-TrkB pathway modulation and vHIP-mPFC neural oscillation reorganization in sub-chronic MK-801 treated mice. Behavioral and Brain Functions. https://doi.org/10.1186/s12993-026-00373-7

Image Credits: AI Generated

DOI: 10.1186/s12993-026-00373-7

Keywords: electroacupuncture, schizophrenia, cognitive impairment, neuroinflammation, BDNF-TrkB, microglia, hippocampus, medial prefrontal cortex, synaptic plasticity, MK-801 mouse model, preclinical study, neural oscillations