Electroacupuncture at the Baihui acupoint alleviates cognitive impairment and exerts neuroprotective effects by modulating the expression and processing of brain-derived neurotrophic factor in APP/PS1 transgenic mice

This experimental study investigated the neuroprotective effects of electroacupuncture at the Baihui point (GV-20) in APP/PS1 transgenic mice, a well-established model of Alzheimer's disease. The research was motivated by the traditional use of this specific point in Chinese medicine to treat cognitive deficits, although the underlying mechanisms remained poorly understood. The study used 40 mice divided into four groups: wild-type control, untreated APP/PS1, APP/PS1 treated with electroacupuncture at Baihui, and APP/PS1 treated at a sham point. The protocol consisted of daily 30-minute sessions for 4 weeks, using dispersive waves at 1 and 20 Hz.

Cognitive assessment was performed using the Morris water maze test, considered the gold standard for spatial memory in rodents. The results demonstrated that APP/PS1 mice showed significant learning and memory deficits, with longer escape times and lower frequency of crossing the original platform location. Notably, electroacupuncture at Baihui significantly reversed these deficits, while sham-point treatment produced no benefits. Pathologic analysis revealed important mechanisms: electroacupuncture dramatically reduced beta-amyloid (1-42) deposition in the hippocampus, one of the main pathologic features of Alzheimer's.

Simultaneously, there was a significant reduction in neuronal apoptosis, evidenced by the decrease in TUNEL-positive cells. The study identified brain-derived neurotrophic factor (BDNF) as a central mediator of the neuroprotective effects. Electroacupuncture increased levels of both mature BDNF and proBDNF, but crucially raised the BDNF/proBDNF ratio, indicating more efficient processing of the protein. This distinction is fundamental, because mature BDNF promotes neuronal survival through the TrkB receptor, whereas proBDNF can induce apoptosis via the p75NTR receptor.

Consistently, the treatment increased TrkB phosphorylation and reduced p75NTR expression, suggesting a shift in signaling balance in favor of neuroprotection. The clinical implications are promising, considering that BDNF is decreased in patients with Alzheimer's and correlates positively with cognitive function. The ability of electroacupuncture to modulate this system represents a biologically plausible mechanism for its therapeutic effects. The study presents methodologic strengths, including the use of a validated transgenic model, appropriate control groups, and comprehensive biomarker analysis.

Limitations include the animal model (which may not fully replicate the complexity of human disease), relatively small sample size, and the need for validation in clinical studies. The specificity of the Baihui point was partially confirmed by the absence of effects with sham-point stimulation, although comparisons with other acupoints would strengthen this conclusion.