Music prevents stress-induced depression and anxiety-like behavior in mice

Depression is a widespread and incurable psychiatric disorder, with stress being a major contributing factor. The rising incidence of depression, fueled by societal pressures and fast-paced lifestyles, necessitates the exploration of alternative, effective therapies with fewer side effects. Current treatments, including pharmaceuticals and gene therapies, are not effective for all patients and may have adverse effects. Music, a form of art that reflects and conveys human emotions, has been hypothesized to alleviate stress and holds potential as a preventative measure against depression. This study aims to investigate the mechanisms by which music may prevent stress-induced depression in mice using a chronic unpredictable mild stress (CUMS) model, examining its effects on the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, inflammation, and neurotrophic factors.

Existing literature highlights the increasing global burden of depression, its complex etiology and symptoms, and the limitations of current treatment approaches. Studies have implicated neurotrophic factors, inflammatory cytokines, the HPA axis, and oxidative stress in the pathophysiology of depression. HPA axis dysfunction, often characterized by elevated cortisol levels, plays a key role. While music therapy is used clinically as an adjunct treatment and shows promise in preventing prenatal depression, research on its mechanisms in preventing stress-induced depression is limited. The researchers reviewed existing literature on the impact of stress on the HPA axis, the role of oxidative stress and inflammation in depression, and the potential benefits of music therapy.

Male C57BL/6 mice were divided into four groups: control, CUMS, Music, and CUMS+Music. CUMS was induced using various stressors for 28 days. The CUMS+Music group was exposed to music for 1.5 hours nightly. A diverse set of 25 musical pieces, spanning various genres and historical periods, was used to stimulate the mice (Table 1). Behavioral tests, including sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), novelty-suppressed feeding (NSF), and elevated plus maze (EPM), were conducted to assess depression- and anxiety-like behaviors. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of various genes related to inflammation (Table 2). Oxidative markers (MDA, GSH-Px, CAT, NO, SOD, corticosterone, and T-AOC) were measured in serum and brain tissues. Immunofluorescence was used to analyze microglia and astrocytes in the dentate gyrus (DG). Statistical analysis was performed using one-way ANOVA followed by Tukey's multiple comparisons test.

Behavioral tests revealed that the CUMS+Music group showed no signs of depression or anxiety, unlike the CUMS group. Music prevented the CUMS-induced changes in locomotor activity, exploration, despair-like behavior, and sucrose preference (Figure 1). Analysis of oxidative stress markers showed that CUMS mice exhibited abnormal levels of NO, SOD, GSH-Px, MDA, and CAT in the serum and brain tissues, while the CUMS+Music group showed normal levels (Figure 2). Similarly, the CUMS+Music group showed normal levels of inflammatory factors (IL-6, IL-1β, iNOS, TNF-α, TGF-β, and IL-10) in brain tissues, unlike the CUMS group (Figures 3, 4). Immunofluorescence analysis demonstrated that music prevented the increase in microglia and astrocytes in the DG of CUMS mice (Figure 4). Furthermore, music prevented CUMS-induced neuronal death and promoted neurogenesis in the DG, evidenced by MAP2 and DCX expression (Figure 4). Finally, music prevented HPA axis activation, as indicated by restored corticosterone and BDNF levels in the brain (Figure 5).

The findings demonstrate that music effectively prevents stress-induced depression and anxiety-like behaviors in mice. The protective effects of music seem to be mediated by its ability to restore HPA axis homeostasis, prevent oxidative stress and inflammation, and maintain neurotrophic factor levels. The study provides preclinical evidence supporting the potential use of music as a preventative intervention for depression. The observed effects on the HPA axis, oxidative stress, inflammation, and neurogenesis suggest multiple mechanisms by which music exerts its beneficial effects on the brain.

This study provides the first preclinical evidence that music can effectively prevent stress-induced depression and anxiety-like behaviors in mice. The protective mechanism likely involves the modulation of HPA axis activity, oxidative stress, and neuroinflammation. Further research is needed to explore the clinical implications of these findings and investigate the potential of music as a natural method for preventing depression in humans. Future studies should investigate the effects in female mice, examine the effects of music played during the day, and analyze the auditory cortex gene expression in response to music.

This study used only male mice, limiting the generalizability of the findings to females. The CUMS was induced during the day, while music was played at night, which may not fully reflect the natural circadian rhythm of the mice. Finally, this study did not evaluate the auditory cortex gene expression profile in response to music, limiting a complete understanding of the effect of music.