Transcranial Magneto-Acoustic Stimulation Protects Synaptic Rehabilitation from Amyloid-Beta Plaques via Regulation of Microglial Functions.

Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic-acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aß) plaque and synaptic plasticity in Alzheimer's disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aß. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aß plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer's disease.

Graphene oxide enhances ß-amyloid clearance by inducing autophagy of microglia and neurons.

Alzheimer's disease (AD) is a common neurodegenerative disease, and its pathogenesis is closely related to ß-amyloid (Aß) peptide. The deposition of Aß in the brain due to impaired Aß clearance is considered as an important cause of AD. The decrease in Aß clearance is closely related to the autophagy dysfunction in brains of AD patients. It is feasible to treat AD by increasing the autophagy level of cells such as microglia and neurons to accelerate Aß clearance. In this article we explored the ability of graphene oxide (GO) to clear Aß through activating autophagy. Our work demonstrated that GO could inhibit the mTOR signaling pathway by activating AMPK to induce the autophagy of microglial and neurons. As expected, with the improvement of autophagy ability of microglia, GO promoted microglia-mediated Aß phagocytosis. Under the conditions of co-culture of microglia and neurons, GO induced the autophagy of microglia and neurons, especially the autophagy of microglia, thereby promoting the clearance of Aß, and ultimately achieved the effect of protecting neurons. Moreover, GO was not only non-cytotoxic to microglia and neurons but also able to reduce the toxicity of Aß to neurons through its clearance. These results have shown the potential of GO in treating Alzheimer's disease.