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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
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作者 Alexander V.Romashchenko Dmitrii V.Petrovskii +15 位作者 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 《Nano Research》 SCIE EI CSCD 2023年第5期7119-7133,共15页
Nanoparticles(NPs)can be transported via the nose-to-brain(N_(2)B)route.Nonetheless,quantitative data on their spatiotemporal dynamics and regulation of the N_(2)B transport are largely lacking.We surveyed metal oxide... Nanoparticles(NPs)can be transported via the nose-to-brain(N_(2)B)route.Nonetheless,quantitative data on their spatiotemporal dynamics and regulation of the N_(2)B transport are largely lacking.We surveyed metal oxide/hydroxide NPs as magnetic resonance imaging(MRI)contrasts for quantitative N_(2)B tracking.NPs containing divalent transition metals were the only ones capable of N_(2)B transmission.Using 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 trajectory.Within 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 ORNs.The NPs’axonal transport is dependent on neuronal activity and microtubule integrity.The Mn_(3)O_(4)-NPs were trans-synaptically transmitted through at least four synapses across the olfactory tract.Trans-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/elimination.Absolute 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 activity.Accordingly,olfactory stimuli(2,5-dimethylpyrazine and acetophenone)significantly modulated and rerouted the Mn_(3)O_(4)-NP N_(2)B transport odor specifically.Finally,the NPs’trans-synaptic transmission was impaired by aging and the onset of Parkinson’s disease.These data suggest new approaches to diagnostics,functional neuroimaging,controlling N_(2)B drug delivery. 展开更多
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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