Quantitative Tracking of trans-Synaptic Nose-to-Brain Transport of Nanoparticles and Its Modulation by Odor, Aging, and Parkinson’s Disease | Sciact - CRIS-система Института катализа

Quantitative Tracking of trans-Synaptic Nose-to-Brain Transport of Nanoparticles and Its Modulation by Odor, Aging, and Parkinson’s Disease Научная публикация

Журнал

NANO RESEARCH
ISSN: 1998-0124 , E-ISSN: 1998-0000

Вых. Данные

Год: 2023, Том: 16, Номер: 5, Страницы: 7119–7133 Страниц : 15 DOI: 10.1007/s12274-022-5302-6

Ключевые слова

Mn3O4 nanoparticles; magnetic resonance imaging (MRI); nose-to-brain transport; trans-synaptic transmission; olfactory stimulation

Авторы

Romashchenko Alexander V. ^1,2,8 , Petrovskii Dmitrii V. ¹ , Trotsky Sergey Yu. ³ , Morozova Ksenia N. ¹ , Illarionova Nina B. ¹ , Zhukova Maria V. ⁶ , Kiseleva Elena V. ¹ , Sharapova Marina B. ¹ , Zuev Daniil S. ⁵ , Kuper Konstantin E. ⁴ , Taskaev Sergey Yu. ^3,4 , Kasatova Anna I. ^3,4 , Kasatov Dmitrii A. ^3,4 , Solovieva Olga I. ¹ , Razumov Ivan A. ¹ , Gerlinskaya Ludmila A. ¹ , Moshkin Mikhail P. ¹ , Moshkin Yuri M. ^1,7

Организации

1	The Federal Research Center Institute of Cytology and Genetics, SB RAS, Academician Lavrentiev Avenue, 10, Novosibirsk 630090, Russia
2	International tomography center, Institutskaya st., 3A, Novosibirsk 630090, Russia
3	G. K. Boreskov Institute of Catalysis, SB RAS, Academician Lavrentiev Avenue, 5, Novosibirsk 630090, Russia
4	The Federal Research Center Budker Institute of Nuclear Physics, SB RAS, Academician Lavrentiev Avenue, 11, Novosibirsk 630090, Russia
5	Institute of Computational Technologies, Academician M.A. Lavrentiev avenue, 6, Novosibirsk 630090, Russia
6	Institute of Gene Biology, Russian Academy of Sciences, Moscow 117334, Russia
7	Institute of Molecular and Cellular Biology, SB RAS, Acad. Lavrentiev Ave, 8/2, Novosibirsk 630090, Russia
8	Federal Research Centre of Biological Systems and Agrotechnologies, RAS, st. January 9, 29, Orenburg 460000, Russia

Информация о финансировании (5)

1	Министерство науки и высшего образования Российской Федерации (с 15 мая 2018)	FWNR-2022-0023
2	Министерство науки и высшего образования Российской Федерации (с 15 мая 2018)	0324-2019-0041 (RFMEFI62119X0023)
3	Российский научный фонд	20-16-00078
4	Министерство науки и высшего образования Российской Федерации (с 15 мая 2018)	FWNR-2022-0004
5	Министерство науки и высшего образования Российской Федерации (с 15 мая 2018)	0259-2021-0011

Nanoparticles (NPs) can be transported via the nose-to-brain (N2B) route. Nonetheless, quantitative data on their spatiotemporal dynamics and regulation of the N2B transport are largely lacking. We surveyed metal oxide/hydroxide NPs as magnetic resonance imaging (MRI) contrasts for quantitative N2B tracking. NPs containing divalent transition metals were the only ones capable of N2B transmission. Using T1-weighted (T1W) MRI, we showed that Mn3O4-NPs were readily engulfed by olfactory receptor neurons (ORNs) without disrupting olfactory sensing, and we mapped their N2B trajectory. Within neurons, the Mn3O4-NPs were localized to the cytosol, mitochondria, and vesicles, and moved at mixed fast and slow axonal transport velocities intra- and extra-vesicularly through ORNs. The NPs’ axonal transport is dependent on neuronal activity and microtubule integrity. The Mn3O4-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 Ca2+ 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 Mn3O4-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’ N2B transport with spontaneous neuronal activity. Accordingly, olfactory stimuli (2,5-dimethylpyrazine and acetophenone) significantly modulated and rerouted the Mn3O4-NP N2B 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, and controlling N2B drug delivery.

Romashchenko A.V. , Petrovskii D.V. , Trotsky S.Y. , Morozova K.N. , Illarionova N.B. , Zhukova M.V. , Kiseleva E.V. , Sharapova M.B. , Zuev D.S. , Kuper K.E. , Taskaev S.Y. , Kasatova A.I. , Kasatov D.A. , Solovieva O.I. , Razumov I.A. , Gerlinskaya L.A. , Moshkin M.P. , Moshkin Y.M.
Quantitative Tracking of trans-Synaptic Nose-to-Brain Transport of Nanoparticles and Its Modulation by Odor, Aging, and Parkinson’s Disease
NANO RESEARCH. 2023. V.16. N5. P.7119–7133. DOI: 10.1007/s12274-022-5302-6 WOS WOS Scopus РИНЦ CAPlusCA OpenAlex

Поступила в редакцию:	7 авг. 2022 г.
Принята к публикации:	7 нояб. 2022 г.
Опубликована online:	16 февр. 2023 г.
Опубликована в печати:	1 мая 2023 г.

Web of science:	WOS:000939823200005 \| WOS:001023725400104
Scopus:	2-s2.0-85148106421
РИНЦ:	53845463
Chemical Abstracts:	2023:350073
Chemical Abstracts (print):	182:421369
OpenAlex:	W4321110092

БД	Цитирований
Scopus	5
Web of science	5 5
РИНЦ	4
OpenAlex	7