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Quantitative tracking of trans-synaptic nose-to-brain transport of nanoparticles and its modulation by odor,aging,and Parkinson’s disease

引用

Nano Research 2023年第5期16卷 7119-7133页

作者： Alexander V.Romashchenko Dmitrii V.Petrovskii Sergey Yu.Trotsky Ksenia N.Morozova Nina B.Illarionova Maria V.Zhukova Elena V.Kiseleva Marina B.Sharapova Daniil S.Zuev Konstantin E.Kuper Sergey Yu.Taskaev Anna I.Kasatova Dmitrii A.Kasatov Olga I.Solovieva ivan a.razumov Ludmila A.Gerlinskaya Mikhail P.Moshkin Yuri M.Moshkin The Federal Research Center Institute of Cytology and Genetics SB RASAcademician Lavrentiev Avenue10Novosibirsk 630090Russia International tomography center Institutskaya st.3ANovosibirsk 630090Russia G.K.Boreskov Institute of Catalysis SB RASAcademician Lavrentiev Avenue5Novosibirsk 630090Russia The Federal Research Center Budker Institute of Nuclear Physics SB RASAcademician Lavrentiev Avenue11Novosibirsk 630090Russia Institute of Computational Technologies Academician M.A.Lavrentiev avenue6Novosibirsk 630090Russia Institute of Gene Biology Russian Academy of SciencesMoscow 117334Russia Institute of Molecular and Cellular Biology SB RASAcad.Lavrentiev Ave8/2Novosibirsk 630090Russia Federal Research Centre of Biological Systems and Agrotechnologies RASst.January 929Orenburg 460000Russia

Nanoparticles(NPs)can be transported via the nose-to-brain(N_(2)B)***,quantitative data on their spatiotemporal dynamics and regulation of the N_(2)B transport are largely *** surveyed metal oxide/hydroxide NPs as magnetic resonance imaging(MRI)contrasts for quantitative N_(2)B *** containing divalent transition metals were the only ones capable of N_(2)B *** T1-weighted(T1W)MRI,we showed that Mn_(3)O_(4)-NPs were readily engulfed by olfactory receptor neurons(ORNs)without disrupting olfactory sensing,we mapped their N_(2)B *** neurons,the Mn_(3)O_(4)-NPs were localized to the cytosol,mitochondria,vesicles,moved at mixed fast and slow axonal transport velocities intraand extra-vesicularly through *** NPs’axonal transport is dependent on neuronal activity and microtubule *** Mn_(3)O_(4)-NPs were trans-synaptically transmitted through at least four synapses across the olfactory ***-synaptic transmission of the NPs was dependent on N-type Ca^(2+)channels and NMDA receptors but blocked by GABAB receptor activation.A five-parameter Weibull signal increase/decrease model fitted to the T1W MRI data allowed for estimating kinetic parameters of Mn_(3)O_(4)-NP accumulation/*** and relative accumulation rates,but not elimination,correlated negatively with the number of synapses from ORNs,indicating a coupling of the NPs’N_(2)B transport with spontaneous neuronal ***,olfactory stimuli(2,5-dimethylpyrazine and acetophenone)significantly modulated and rerouted the Mn_(3)O_(4)-NP N_(2)B transport odor ***,the NPs’trans-synaptic transmission was impaired by aging and the onset of Parkinson’s *** data suggest new approaches to diagnostics,functional neuroimaging,controlling N_(2)B drug delivery.

关键词： Mn_(3)O_(4)nanoparticles magnetic resonance imaging(MRI) nose-to-brain transport trans-synaptic transmission olfactory stimulation

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