Piezoelectric nanogenerators enabled neuromodulation rescued dopaminergic neuron loss in Parkinson’s disease

Parkinson's disease (PD) is a neurodegenerative disease with dopaminergic neurons loss, which induces dopamine reduction and body motion disorder. Traditional deep brain stimulation (DBS), which involves the implanting metal electrodes into the subcortical nucleus of the brain, has a huge risk of invasive surgery and low resolution. Here we present that pomegranate-like piezoelectric nanogenerators are able to efficiently transduce ultrasonic wave into electric power generation under ultrasound stimulation, which modulates intracellular calcium signaling and tyrosine hydroxylase levels to activate the neuron activity and process of deep-brain tissue in vitro and in vivo. Strikingly, after one-week nanogenerator-mediated neuromodulation, the damaged dopaminergic neurons in PD-zebrafish and mice were reversed with a decrease in α-synuclein aggregates and an increase in tyrosine hydroxylase for neuronal recovery of PD. The behaviors of PD mice model also have a significant improvement, compared with untreated group. This approach provides a minimally invasive and high precision neurotechnology protect against neuronal death and loss of synapse in PD and other neurodegenerative diseases.