Terahertz photons promote neuron growth and synapse formation through cAMP signaling pathway

Abstract Neurite outgrowth and synapse formation constitute the cellular basis for the establishment and plasticity of neural networks, crucially involved in cognitive functions. However, the techniques currently available to effectively and specifically modulate these processes remain limited. In this work, we propose a non-drug and non-thermal terahertz (THz) photon modulation approach that enhances neuronal growth and synaptogenesis. Frequency screening experiments show that 34.5 THz photon stimulation could effectively promote neurite elongation and postsynaptic density protein 95 (PSD95) expression by 26.0% in rat hippocampal neurons. Subsequent cellular experiments reveal an upregulation of the cyclic adenosine monophosphate (cAMP) signaling pathway and adenylyl cyclase type 1 (AC1) activity after 34.5 THz photon irradiation. Molecular dynamics simulations suggest that 34.5 THz photons promote the binding between AC1 and ligand, accelerating cAMP generation. In vivo experiments further confirm an increase in hippocampal cAMP levels and dendritic spine density after THz photon stimulation, accompanied by a significant improvement in cognitive performance. Overall, our results suggest THz photon stimulation as an effective and specific method for neuromodulation, promising for future applications in the treatment of cognitive dysfunction.