The role of olfactory transport in the penetration of manganese oxide nanoparticles from blood into the brain

Abstract

There is no doubt that various nanoparticles (NPs) can enter the brain from the nasal cavity. It is assumed that NPs can penetrate from blood into the central nervous system (CNS) only by breaking the blood–brain barrier (BBB). The accumulation of NPs in CNS can provoke many neurological diseases; therefore, the understanding of its mechanisms is of both academic and practical interest. Although hitting from the surface of the lungs into the bloodstream, NPs can accumulate in various mucous membranes, including the nasal mucosa. Thus, we cannot rule out the ability of NPs to be transported from the bloodstream to the brain through the olfactory uptake. To test this hypothesis, we used paramagnetic NPs of manganese oxide (Mn3O4-NPs), whose accumulation patterns in the mouse brain were recorded using T1-weighted magnetic resonance imaging. The effect of intranasal application of endocytosis and axonal transport inhibitors on the brain accumulation patterns of intranasally or intravenously injected Mn3O4-NPs was evaluated. A comparative analysis of the results showed that the transport of Mn3O4-NPs from the nasal cavity to the brain is more efficient than their local permeation through BBB into CNS from the bloodstream, for example with the accumulation of Mn3O4NPs in the dentate gyrus of the hippocampus, and through the capture and transport of NPs from the blood by olfactory epithelium cells. Also, experiments with the administration of chlorpromazine, a specific inhibitor of clathrin-dependent endocytosis, and methyl-β-cyclodextrin, inhibitor of the lipid rafts involved in the capture of substances by endothelium cells, showed differences in the mechanisms of NP uptake from the nasal cavity and from the bloodstream. In this study, we show a significant contribution of axonal transport to NP accumulation patterns in the brain, both from the nasal cavity and from the vascular bed. This explains the accumulation of different sorts of submicron particles (neurotropic viruses, insoluble xenobiotics, etc.), unable to pass BBB, in the brain. The results will add to the understanding of the pathogenesis of various neurodegenerative diseases and help studying the side effects of therapeutics administered intravenously.

To the question of intensification of free radical oxidation of biosubstrates under action of nanosized materials

“…Позитивно заряджені частинки потрапляють у клітини легше, ніж негативно заряджені. Встановлено передислокацію НЧ по нюхових, трійчастих, трахеобронхіальних нервах і нейром'язових з'єднаннях [12]. Експериментально підтверджено проникнення НЧ між клітинами, механічне пошкодження мембран клітини, а також фагоцитоз НЧ клітинами з подальшим переміщенням їх у зовнішнє середовище [13,14].…”

BGRS/SB-2022 681 The role of manganese oxide nanoparticles in the formation of stress granules in the mouse olfactory system

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Motivation and Aim: In recent years, air pollution has increased significantly, and humans, like other terrestrial animals, are constantly exposed to solid aerosols, which may contain various xenobiotics, including nanoparticles (NPs) that can enter the brain from the nasal cavity [1]. Moreover, it was shown that the addition of nanoparticles to the cellular environment induces the formation of stress granules (SG), which are the cellular response to stress [2].

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Nanoparticle axonal transport assessment in neurodegeneration susceptible mice strain

“…Therefore a noninvasive method to assess axonal transport rate could potentially allow for early diagnosis of such diseases. Earlier it was shown that Mn3O4 nanoparticles (Mn3O4-NP) can act as an magnetic resonance imaging (MRI) contrast, that upon intranasal injection can be engulfed by olfactory neurons, and subsequently get transported into the deeper brain areas [3]. In this study we have assessed Mn3O4-NP spreading in brain of two congenic mice strains: C57Bl and B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle (with high α-synucleinopathy risk, motor impairments become evident at the age of 12 months [4]).…”

“…Each group consisted of 6 males. Mn3O4-NP were prepared as previously described [3]. They were suspended in saline and intranasally instilled.…”