Modulating basal ganglia circuitry is of great signifcance in the improvement of motor function in Parkinson’s disease(PD).Here,for the frst time,we demonstrate that noninvasive ultrasound deep brain stimulation(UDBS...Modulating basal ganglia circuitry is of great signifcance in the improvement of motor function in Parkinson’s disease(PD).Here,for the frst time,we demonstrate that noninvasive ultrasound deep brain stimulation(UDBS)of the subthalamic nucleus(STN)or the globus pallidus(GP)improves motor behavior in a subacute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Immunohistochemical c-Fos protein expression confrms that there is a relatively high level of c-Fos expression in the STN-UDBS and GP-UDBS group compared with sham group(both p<0.05).Furthermore,STN-UDBS or GPUDBS signifcantly increases the latency to fall in the rotarod test on day 9(p<0.05)and decreases the time spent climbing down a vertical rod in the pole test on day 12(p<0.05).Moreover,our results reveal that STN-UDBS or GP-UDBS protects the dopamine(DA)neurons from MPTP neurotoxicity by downregulating Bax(p<0.001),upregulating Bcl-2(p<0.01),blocking cytochrome c(Cyt C)release from mitochondria(p<0.05),and reducing cleaved-caspase 3 activity(p<0.01)in the ipsilateral substantia nigra(SN).Additionally,the safety of ultrasound stimulation is characterized by hematoxylin and eosin(HE)and Nissl staining;no hemorrhage or tissue damage is detected.Tese data demonstrate that UDBS enables modulation of STN or GP neural activity and leads to neuroprotection in PD mice,potentially serving as a noninvasive strategy for the clinical treatment of PD.展开更多
Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness(DOC).However,these treatments require invasive procedures.This report presents a noninv...Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness(DOC).However,these treatments require invasive procedures.This report presents a noninvasive strategy to stimulate central nervous system neurons selectively for recovery from DOC in mice.Through the delivery of ultrasound energy to the ventral tegmental area,mice were aroused from an unconscious,anaesthetized state in this study,and this process was controlled by adjusting the ultrasound parameters.The mice in the sham group under isoflurane-induced,continuous,steady-state general anaesthesia did not regain their righting reflex.On insonation,the emergence time from inhaled isoflurane anaesthesia decreased(sham.13.63±0.53 min,ultrasound.1.5±0.19 min,p<0.001).Further,the induction time(sham.12.0±0.6 min,ultrasound.17.88±0.64 min,p<0.001)and the concentration for 50%of the maximal effect(EC50)of isoflurane(sham.0.6%,ultrasound.0.7%)increased.In addition,ultrasound stimulation reduced the recovery time in mice with traumatic brain injury(sham.30.38±1.9 min,ultrasound.7.38±1.02 min,p<0.01).This noninvasive strategy could be used on demand to promote emergence from DOC and may be a potential treatment for such disorders.展开更多
Ultrasound stimulation is an emerging noninvasive option in treating neuropsychiatric disorders. The present study investigates the behavioral alterations resulting from ultrasound stimulation on the nucleus accumbens...Ultrasound stimulation is an emerging noninvasive option in treating neuropsychiatric disorders. The present study investigates the behavioral alterations resulting from ultrasound stimulation on the nucleus accumbens(NAc) in freely moving mice. Our results show that an acute ultrasound stimulation on the NAc, rather than the visual cortex or auditory cortex, led to a pronounced avoidance behavior, while repeated NAc ultrasound stimulation resulted in an obvious conditioned place aversion with changes in synaptic protein(Glu A1/2 subunit) expression. Notably, NAc ultrasound stimulation suppressed the morphine-induced conditioned place preference. The results provide evidence that NAc ultrasound stimulation can be applied as a potential noninvasive therapeutic option in treating psychiatric disorders.展开更多
基金We wish to thank Dr.Jun Jia(Capital Medical University)for assisting us with experimental design and Dr.Yunhui Liu(Shenzhen Institutes of Advanced Technology)for technical guidance.This work was supported by the National Natural Science Foundation of China(Grants nos.81527901,11534013,11774371,11574341,11674347,and 11874381)Natural Science Foundation of Guangdong Province(2017B030306011)Youth Innovation Promotion Association CAS(2018393).
文摘Modulating basal ganglia circuitry is of great signifcance in the improvement of motor function in Parkinson’s disease(PD).Here,for the frst time,we demonstrate that noninvasive ultrasound deep brain stimulation(UDBS)of the subthalamic nucleus(STN)or the globus pallidus(GP)improves motor behavior in a subacute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Immunohistochemical c-Fos protein expression confrms that there is a relatively high level of c-Fos expression in the STN-UDBS and GP-UDBS group compared with sham group(both p<0.05).Furthermore,STN-UDBS or GPUDBS signifcantly increases the latency to fall in the rotarod test on day 9(p<0.05)and decreases the time spent climbing down a vertical rod in the pole test on day 12(p<0.05).Moreover,our results reveal that STN-UDBS or GP-UDBS protects the dopamine(DA)neurons from MPTP neurotoxicity by downregulating Bax(p<0.001),upregulating Bcl-2(p<0.01),blocking cytochrome c(Cyt C)release from mitochondria(p<0.05),and reducing cleaved-caspase 3 activity(p<0.01)in the ipsilateral substantia nigra(SN).Additionally,the safety of ultrasound stimulation is characterized by hematoxylin and eosin(HE)and Nissl staining;no hemorrhage or tissue damage is detected.Tese data demonstrate that UDBS enables modulation of STN or GP neural activity and leads to neuroprotection in PD mice,potentially serving as a noninvasive strategy for the clinical treatment of PD.
基金supported by the National Natural Science Foundation of China(Grant No.11904380,No.81771430)Guangdong Grant“Key Technologies for Treatment of Brain Disorders”(No.2018B030332001,No.2018B030331001)+1 种基金Shenzhen Basic Science Research(JCYJ20200109105622824,JCYJ20200109110006136)Youth Innovation Promotion Association CAS(2018393,2020358).
文摘Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness(DOC).However,these treatments require invasive procedures.This report presents a noninvasive strategy to stimulate central nervous system neurons selectively for recovery from DOC in mice.Through the delivery of ultrasound energy to the ventral tegmental area,mice were aroused from an unconscious,anaesthetized state in this study,and this process was controlled by adjusting the ultrasound parameters.The mice in the sham group under isoflurane-induced,continuous,steady-state general anaesthesia did not regain their righting reflex.On insonation,the emergence time from inhaled isoflurane anaesthesia decreased(sham.13.63±0.53 min,ultrasound.1.5±0.19 min,p<0.001).Further,the induction time(sham.12.0±0.6 min,ultrasound.17.88±0.64 min,p<0.001)and the concentration for 50%of the maximal effect(EC50)of isoflurane(sham.0.6%,ultrasound.0.7%)increased.In addition,ultrasound stimulation reduced the recovery time in mice with traumatic brain injury(sham.30.38±1.9 min,ultrasound.7.38±1.02 min,p<0.01).This noninvasive strategy could be used on demand to promote emergence from DOC and may be a potential treatment for such disorders.
基金supported by the National Natural Science Foundation of China(81527901,81822017,11534013,11774371,31771215)Youth Innovation Promotion Association CAS(2018393)+1 种基金sponsored by the Science and Technology Commission of Shanghai Municipality(18QA1403700,18JC1420304,18140901700)Shanghai Clinical Research Center for Mental Health(19MC1911100)。
文摘Ultrasound stimulation is an emerging noninvasive option in treating neuropsychiatric disorders. The present study investigates the behavioral alterations resulting from ultrasound stimulation on the nucleus accumbens(NAc) in freely moving mice. Our results show that an acute ultrasound stimulation on the NAc, rather than the visual cortex or auditory cortex, led to a pronounced avoidance behavior, while repeated NAc ultrasound stimulation resulted in an obvious conditioned place aversion with changes in synaptic protein(Glu A1/2 subunit) expression. Notably, NAc ultrasound stimulation suppressed the morphine-induced conditioned place preference. The results provide evidence that NAc ultrasound stimulation can be applied as a potential noninvasive therapeutic option in treating psychiatric disorders.
基金supported by financial support from the National Key Research and Development Program of China(2021YFF1200200)the National Natural Science Foundation of China(22161132008)+2 种基金the Natural Science Foundation of Shanghai,China(19520714100 and 19ZR1475800)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SNZJU-SIAS-006)the Natural Science Foundation of Zhejiang Province(LQ21C050001)。
