Antidepressant-Like Effects of Acupuncture: Insights From DNA Methylation and Histone Modifications of Brain-Derived Neurotrophic Factor

Depression is one of the most prevalent psychiatric conditions in the world, representing a leading cause of functional disability. Chronic stress is recognized as one of the most important factors in the development, maintenance, and worsening of depression, and can cause profound alterations in brain function, impair the formation of new neurons, and modify synaptic function. Among the mechanisms involved in depression, the significant reduction in the expression of brain-derived neurotrophic factor, known as BDNF, stands out — a protein essential for the development and functioning of the nervous system. This protein is widely distributed in the brain, including areas such as the hippocampus, cerebral cortex, and limbic system structures, and is fundamental to processes of learning, memory, and the formation of neural circuits.

This study investigated the mechanisms by which acupuncture may exert antidepressant effects, focusing specifically on epigenetic modifications of the BDNF gene. The research used a model of depression in rats induced by social isolation and chronic unpredictable mild stress, a well-established methodology that faithfully reproduces the symptoms of human depression. The animals were divided into four groups: control, depression model, treatment with fluoxetine (a standard antidepressant medication), and treatment with acupuncture. Acupuncture treatment was performed at the Baihui (百會) and Yintang (印堂) points, located in the head region, for 28 consecutive days.

The researchers used several advanced laboratory techniques to measure BDNF protein expression in blood and hippocampus, assess histone modifications, and examine DNA methylation patterns in the promoter region of the BDNF gene.

The results showed that chronic stress caused a significant reduction in BDNF protein in both the blood and the hippocampus of the animals, accompanied by typical depression-like behaviors such as reduced pleasure, decreased locomotor activity, and weight loss. Notably, acupuncture was able to reverse these alterations, restoring BDNF levels and improving depressive behaviors in a manner comparable to fluoxetine. The study revealed that stress elevated HDAC2 levels, an enzyme that participates in gene regulation, and reduced acetylation of histone H3K9, a marker associated with gene activation. Acupuncture was able to normalize these epigenetic markers, promoting an environment more favorable to BDNF gene expression.

Interestingly, although no significant differences were found in DNA methylation patterns in the BDNF promoter region, histone modifications proved to be fundamental in explaining the beneficial effects of acupuncture.

For patients suffering from depression, these findings are particularly relevant, as they offer solid scientific evidence that acupuncture can be an effective therapeutic alternative. The study demonstrates that acupuncture not only alleviates depressive symptoms but also acts at the molecular level, correcting fundamental biochemical alterations associated with the disease. For health professionals, these results provide a scientific basis for incorporating acupuncture as a complementary or alternative treatment for depression, especially considering that the effects observed were similar to those of conventional antidepressant medications. The research also suggests that blood BDNF levels may serve as biomarkers to monitor both the severity of depression and the efficacy of acupuncture treatment, offering an objective tool to assess therapeutic response.

The study presents some important limitations that should be considered in interpreting the results. The absence of a specific control group for acupuncture, using nonspecific points or sham acupuncture, limits the ability to determine whether the observed effects are specific to the acupuncture points used. In addition, the investigation focused only on the promoter I region of the BDNF gene, while other regulatory regions may also be involved in the mechanisms of depression. The fact that no significant differences in DNA methylation were found suggests that other regulatory mechanisms, such as microRNAs or post-transcriptional modifications, may be contributing to the observed effects.

Despite these limitations, this work represents an important advance in understanding the molecular mechanisms of acupuncture in the treatment of depression, providing evidence that this ancient therapy acts through specific and measurable biological pathways, which may contribute to its greater acceptance and integration into contemporary medical practice.