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

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.

Use of nanoscale metals in poultry diet as a mineral feed additive

The research was aimed at studying the efficiency of a nanoscale alloy of copper(Cu) and zinc(Zn) to be used as a mineral additive for feeding broiler chickens,compared to inorganic and organic forms of these elements.Biochemical studies of the blood serum were performed using an automated analyzer.The mineral composition was determined by atomic emission and mass spectrometry(MS-ISP),The study was performed on broiler chickens of cross Smena 7(n=72) in the conditions of a vivarium.There were3 treatment groups with 24 chickens in each.Replacing the inorganic form of mineral supplements with the nanosized alloy resulted in a positive productive effect,with a tendency to increasing the content of serum protein.The nano scale form of metals improved(P <0.05) the activity of aminotransferases.At the same time,the liver micro structure of experimental groups is similar to that of the control.There was a moderate plethora and poor polymorphoncellular infiltration around the interlobular triads with a clear morphological orga nization of the stromal and parenchymal co mponents of the liver.However,the lack of oxidative stress was confirmed by the dynamics of catalase(CT),total superoxide dismutase(TSOD) and malondialdehyde(MDA) levels,and the concentrations of which did not exceed the reference level Replacing Cu and Zn sulfates with the nanoscale alloy(group 1) and organic form(group 2) of these elements in the diet of broiler chickens was accompanied by the increasing pool of these elements in the organisms at the end of the experiment.Copper was accumulated throughout the experiment in experimental group 1,compared to the reference,with the maximum difference in the liver of 36.5%(P ≤ 0.05),in the feathers 2.5 times(P ≤ 0.01).Assessment of the Zn level dynamics in the feathers revealed a well noticeable tendency to reducing its concentrations during the experiment in all groups.Against the background of feeding a nanoscale alloy,Zn concentration in the liver exceeded the reference by 66.8%(P ≤ 0.01) only at the end of the experiment.Thus,nanoscale forms of Cu and Zn have a cumulative effect,and may become an alternative to inorganic and organic forms of these elements in poultry nutrition.