Music intervention as a therapeutic approach to cognitive impairments in APP/PS1 mice

Alzheimer's disease (AD) is typified by progressive deterioration in memory and executive capacities. Although music-based interventions represent a promising non-pharmacological strategy for AD, the underlying mechanisms remain insufficiently understood. APP/PS1 transgenic mice were subjected to 30 consecutive days of musical stimulation, with wild-type C57BL/6 J and untreated APP/PS1 mice serving as controls. Neurobehavioral assessments revealed that music intervention substantially improved memory performance in transgenic AD mice. Mechanistically, music attenuated oxidative stress in both serum and hippocampus of APP/PS1 mice, as evidenced by decreased nitric oxide (NO) and malondialdehyde (MDA) levels along with enhanced antioxidant activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC). Peripheral and hippocampal inflammatory responses were also effectively inhibited following musical treatment. Music restored synaptic plasticity-related protein expression, increased postsynaptic density thickness, narrowed synaptic cleft, and elevated dendritic spine density. Additionally, music exposure alleviated Aβ deposition and neuronal loss in APP/PS1 mice. These findings indicate that music-based auditory enrichment exerts neuroprotective effects against AD through synergistically modulating oxidative stress, neuroinflammation, synaptic plasticity, and neuronal survival, providing mechanistic insights into its intervention potential for AD.