An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
Diamond-like AgGaS_(2)(DL AGS),as the typical infrared nonlinear optical(IR NLO)material,has suffered from its intrinsic drawbacks like narrow band gap(E_(g))and low laser-induced damage threshold(LIDT).In this work,b...Diamond-like AgGaS_(2)(DL AGS),as the typical infrared nonlinear optical(IR NLO)material,has suffered from its intrinsic drawbacks like narrow band gap(E_(g))and low laser-induced damage threshold(LIDT).In this work,by first introducing[NaS_(8)]polyhedral unit into the A_(2)^(Ⅰ)Q^(Ⅵ)-Ag_(2)Q^(Ⅵ)-C_(2)^(Ⅲ)Q_(3)^(Ⅵ) system,a new Ag-based sulfide NaAg_(3)Ga_(8)S_(14) with diamond-like framework(DLF)has been successfully synthesized via a high-temperature solid-state method in experiment.The compound shows a wide Eg(~3.0 eV),high LIDT(3.0×AGS)and moderate phase-matching NLO response(~0.7×AGS),effectively balancing the E_(g)(≥3.0 eV)and NLO response(≥0.5×AGS),demonstrating its promise for IR NLO applications.Theoretical calculations elucidate the orbital hybridization between Na 3s,Ag 4d5s and S 3p enhances E_(g),and the aligned NLO-active units([AgS_(4)]and[GaS_(4)])induce moderate NLO response in the compound.These findings not only expand the chemical and structural diversities of Ag-based chalcogenides,but also provide effective strategies for designing DLF functional materials derived from diamond-like structures.展开更多
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
基金supported by the Tianshan Talent Training Program(2024TSYCLJ0035)the Natural Science Foundation of the Xinjiang Uygur Autonomous Region(2024D01E30,2025D01B157)+3 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0880000)the Open Fund of the Anhui Key Laboratory of Photonic Materials and Devices(AHKL2024KF02)the National Natural Sci-ence Foundation of China(22475234,52402017)the support from Tianchi Doctor Plan of Xinjiang Uygur Autonomous Region.
文摘Diamond-like AgGaS_(2)(DL AGS),as the typical infrared nonlinear optical(IR NLO)material,has suffered from its intrinsic drawbacks like narrow band gap(E_(g))and low laser-induced damage threshold(LIDT).In this work,by first introducing[NaS_(8)]polyhedral unit into the A_(2)^(Ⅰ)Q^(Ⅵ)-Ag_(2)Q^(Ⅵ)-C_(2)^(Ⅲ)Q_(3)^(Ⅵ) system,a new Ag-based sulfide NaAg_(3)Ga_(8)S_(14) with diamond-like framework(DLF)has been successfully synthesized via a high-temperature solid-state method in experiment.The compound shows a wide Eg(~3.0 eV),high LIDT(3.0×AGS)and moderate phase-matching NLO response(~0.7×AGS),effectively balancing the E_(g)(≥3.0 eV)and NLO response(≥0.5×AGS),demonstrating its promise for IR NLO applications.Theoretical calculations elucidate the orbital hybridization between Na 3s,Ag 4d5s and S 3p enhances E_(g),and the aligned NLO-active units([AgS_(4)]and[GaS_(4)])induce moderate NLO response in the compound.These findings not only expand the chemical and structural diversities of Ag-based chalcogenides,but also provide effective strategies for designing DLF functional materials derived from diamond-like structures.
