Cognitive improvement via a modulated rhythmic pulsed magnetic field in D-galactose-induced accelerated aging mice

[Display omitted] •A modulated pulsed magnetic field (PMF) containing both theta and gamma rhythms was conducted to perform whole brain stimulation on rodents.•Accelerated aging mice via chronic D-gal injection presented declined learning and memory abilities, as well as neuron degeneration especially in hippocampal CA3 area.•Modulated PMF stimulation during aging process enhanced the cognitive behavior performances of D-gal-induced aging mice.•Hippocampal neuron degeneration induced by D-gal could be partially rescued by the modulated PMF. Rhythmic physical stimulations have emerged as effective noninvasive intervention strategies in the treatment of pathological cognitive deficits. Transcranial magnetic stimulation (TMS) can regulate neural firing and improve the learning and memory abilities of rodents or patients with cognitive deterioration. However, the effects of elaborate magnetic stimulation with low intensity during aging or other neurological disordering processes on cognitive decline remain unclear. In this study, we developed an elaborate modulated pulsed magnetic field (PMF) stimulation with a complex pattern in the theta repeated frequency and gamma carrier frequency and then determined the effects of this rhythmic PMF on the cognitive function of accelerated aging mice established by chronic subcutaneous injection of D-galactose (D-gal). The results of the Morris water maze (MWM) test showed that mice treated with modulated PMF displayed shorter swimming distance and latency time in the spatial exploration acquisition trial and exhibited a significant preference in the target presumptive platform area in the probe trial, all of which indicated the enhancement in spatial learning and memory abilities upon PMF stimulation of the accelerated aging mice. The novel object recognition (NOR) test results showed a similar tendency as the MWM results although without statistical significance. Further determination of histological structures demonstrated that the cognitive function-related hippocampal CA3 neurons degenerated upon D-gal injection, which could also be partially rescued by PMF application. In comparison with the high-intensity TMS approach, low-intensity magnetic stimulation could be much safer and allow deeper penetration without adverse effects such as seizure. In summary, modulated PMF, even with low intensity, could effectively improve rodent cognitive functions impaired by D-gal-induced accelerated aging, which might provide a new