Ultrasound(US)has emerged as a noninvasive neurostimulation method for motor control in Parkinson’s disease(PD).Previous in vivo US neuromodulation studies for PD were single-target stimulation.However,the motor symp...Ultrasound(US)has emerged as a noninvasive neurostimulation method for motor control in Parkinson’s disease(PD).Previous in vivo US neuromodulation studies for PD were single-target stimulation.However,the motor symptoms of PD are linked with neural circuit dysfunction,and multi-target stimulation is conducted in clinical treatment for PD.Thus,in the present study,we achieved multi-target US stimulation using holographic lens transducer based on the Rayleigh–Sommerfeld diffraction integral and time-reversal methods.We demonstrated that holographic US stimulation of the bilateral dorsal striatum(DS)could improve the motor function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of PD.The holographic US wave(fundamental frequency:3 MHz,pulse repetition frequency:500 Hz,duty cycle:20%,tone-burst duration:0.4 ms,sonication duration:1 s,interstimulus interval:4 s,spatial-peak temporal-average intensity:180 mw/cm2)was delivered to the bilateral DS 20 min per day for consecutive 10 d after the last injection of MPTP.Immunohistochemical c-Fos staining demonstrated that holographic US significantly increased the c-Fos-positive neurons in the bilateral DS compared with the sham group(P=0.003).Moreover,our results suggested that holographic US stimulation of the bilateral DS ameliorated motor dysfunction(P<0.05)and protected the dopaminergic(DA)neurons(P<0.001).The neuroprotective effect of holographic US was associated with the prevention of axon degeneration and the reinforcement of postsynaptic densities[growth associated protein-43(P<0.001),phosphorylated Akt(P=0.001),β3-tubulin(P<0.001),phosphorylated CRMP2(P=0.037),postsynaptic density(P=0.023)].These data suggested that holographic US-induced acoustic radiation force has the potential to achieve multi-target neuromodulation and could serve as a reliable tool for the treatment of PD.展开更多
基金supported,in part,by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0930000)the National Natural Science Foundation of China(nos.T2122023,U23A20479,12227809,and 12104478)+1 种基金the Natural Science Foundation of Guangdong Province(no.202381515040008)Shenzhen Basic Science Research(nos.JCYJ20220818101608018,20231123154444001,and 20220812171109001).
文摘Ultrasound(US)has emerged as a noninvasive neurostimulation method for motor control in Parkinson’s disease(PD).Previous in vivo US neuromodulation studies for PD were single-target stimulation.However,the motor symptoms of PD are linked with neural circuit dysfunction,and multi-target stimulation is conducted in clinical treatment for PD.Thus,in the present study,we achieved multi-target US stimulation using holographic lens transducer based on the Rayleigh–Sommerfeld diffraction integral and time-reversal methods.We demonstrated that holographic US stimulation of the bilateral dorsal striatum(DS)could improve the motor function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of PD.The holographic US wave(fundamental frequency:3 MHz,pulse repetition frequency:500 Hz,duty cycle:20%,tone-burst duration:0.4 ms,sonication duration:1 s,interstimulus interval:4 s,spatial-peak temporal-average intensity:180 mw/cm2)was delivered to the bilateral DS 20 min per day for consecutive 10 d after the last injection of MPTP.Immunohistochemical c-Fos staining demonstrated that holographic US significantly increased the c-Fos-positive neurons in the bilateral DS compared with the sham group(P=0.003).Moreover,our results suggested that holographic US stimulation of the bilateral DS ameliorated motor dysfunction(P<0.05)and protected the dopaminergic(DA)neurons(P<0.001).The neuroprotective effect of holographic US was associated with the prevention of axon degeneration and the reinforcement of postsynaptic densities[growth associated protein-43(P<0.001),phosphorylated Akt(P=0.001),β3-tubulin(P<0.001),phosphorylated CRMP2(P=0.037),postsynaptic density(P=0.023)].These data suggested that holographic US-induced acoustic radiation force has the potential to achieve multi-target neuromodulation and could serve as a reliable tool for the treatment of PD.
