Inhaled Lead Nanoparticles Enter the Brain through the
Olfactory Pathway and Induce Neurodegenerative Changes
Resembling Tauopathies

J 2025

Inhaled Lead Nanoparticles Enter the Brain through the Olfactory Pathway and Induce Neurodegenerative Changes Resembling Tauopathies

JEDLIČKOVÁ, Adriena; Daniela KRISTEKOVÁ; Zuzana HUSÁKOVÁ; Pavel COUFALÍK; Lucie VRLÍKOVÁ et al.

Základní údaje

Originální název

Inhaled Lead Nanoparticles Enter the Brain through the Olfactory Pathway and Induce Neurodegenerative Changes Resembling Tauopathies

Autoři

Vydání

ACS Nano, American Chemical Society, 2025, 1936-0851

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30108 Toxicology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 16.000 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

BBB; clearance ability; cytoskeleton; mTOR; nanotoxicity; neurodegeneration diseases; tau

Štítky

14110517, 14313010, 14314010, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 9. 2025 09:09, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

Lead nanoparticles (PbNPs) in air pollution pose a significant threat to human health, especially due to their neurotoxic effects. In this study, we exposed mice to lead(II) oxide nanoparticles (PbONPs) in inhalation chambers to mimic real-life exposure and assess their impact on the brain. PbONPs caused the formation of Hirano bodies and pathological changes related to neurodegenerative disorders through cytoskeletal disruptions without the induction of inflammation. Damage to astrocytic endfeet and capillary endothelial cells indicated a compromised blood-brain barrier (BBB), allowing PbONPs to enter the brain. Additionally, NPs were detected along the olfactory pathway, including fila olfactoria, suggesting that at least a proportion of PbNPs enter the brain directly by passing through the olfactory epithelium. PbNP inhalation severely damaged the apical parts of olfactory epithelial cells, including the loss of microtubules in their ciliary distal segments. Inhalation of PbONPs led to the rapid accumulation of lead in the brain, while more soluble lead(II) nitrate NPs did not accumulate significantly until 11 weeks of exposure. PbNPs induced disruption of the BBB at multiple levels, ranging from ultrastructural changes to functional impairments of the barrier; however, they did not induce systemic inflammation in the brain. The clearance ability of the brain to remove Pb was very low for both types of NPs, with significant pathological effects persisting even after a long clearance period. Cation-binding proteins (ZBTB20 and calbindin1) were distributed unevenly in the brain, with the strongest signal located in the hippocampus, which exhibited the greatest defects in nuclear architecture, indicating that this area is the most sensitive structure for PbNP exposure. PbNP exposure also altered the PI3K/Akt/mTOR signaling pathway, and tau phosphorylation in the hippocampus and inhibition of tau phosphorylation by GSK-3 inhibitor rescued the negative effect of PbONPs on the intracellular calcium level in trigeminal ganglion cultures. In zebrafish larvae, PbONPs affected locomotor activity and reduced calcium levels in the medium enhanced negative effect of PbONP on animal mobility, even increasing lethality. These findings suggest that cytoskeletal disruption and calcium dysregulation are key factors in PbNP-induced neurotoxicity, providing potential targets for therapeutic intervention to prevent neurodegenerative changes following PbNP exposure.

Návaznosti

GA20-02203S, projekt VaV

Název: Analýza tkáňové odpovědi na inhalaci nanočástic kovů a mechanismus jejich čištění

Investor: Grantová agentura ČR, Analysis of tissue response to metal nanoparticles inhalation and mechanisms of their clearance

GA24-10051S, projekt VaV

Název: Vliv nanočástic kovů na plicní tkáně a buněčné procesy přispívající k jejich efluxu z těchto tkání

Investor: Grantová agentura ČR, Vliv nanočástic kovů na plicní tkáně a buněčné procesy přispívající k jejich efluxu z těchto tkání

Citovat

JEDLIČKOVÁ, Adriena; Daniela KRISTEKOVÁ; Zuzana HUSÁKOVÁ; Pavel COUFALÍK; Lucie VRLÍKOVÁ; Tereza SMUTNÁ; Michaela CAPANDOVÁ; Lukáš ALEXA; Denisa LUSKOVÁ; Kamil KŘŮMAL; Veronika JAKEŠOVÁ; Zbyněk VEČEŘA; Nikodém ZEZULA; Viktor KANICKÝ; Aleš HAMPL; Tomáš VACULOVIČ; Pavel MIKUŠKA; Jana DUMKOVÁ a Marcela BUCHTOVÁ. Inhaled Lead Nanoparticles Enter the Brain through the Olfactory Pathway and Induce Neurodegenerative Changes Resembling Tauopathies. ACS Nano. American Chemical Society, 2025, roč. 19, č. 13, s. 12799-12826. ISSN 1936-0851. Dostupné z: https://doi.org/10.1021/acsnano.4c14571.

@article{2496047,
   author = {Jedličková, Adriena and Kristeková, Daniela and Husáková, Zuzana and Coufalík, Pavel and Vrlíková, Lucie and Smutná, Tereza and Capandová, Michaela and Alexa, Lukáš and Lusková, Denisa and Křůmal, Kamil and Jakešová, Veronika and Večeřa, Zbyněk and Zezula, Nikodém and Kanický, Viktor and Hampl, Aleš and Vaculovič, Tomáš and Mikuška, Pavel and Dumková, Jana and Buchtová, Marcela},
   article_number = {13},
   doi = {https://doi.org/10.1021/acsnano.4c14571},
   keywords = {BBB; clearance ability; cytoskeleton; mTOR; nanotoxicity; neurodegeneration diseases; tau},
   language = {eng},
   issn = {1936-0851},
   journal = {ACS Nano},
   title = {Inhaled Lead Nanoparticles Enter the Brain through the Olfactory Pathway and Induce Neurodegenerative Changes Resembling Tauopathies},
   url = {https://pubs.acs.org/doi/10.1021/acsnano.4c14571},
   volume = {19},
   year = {2025}
}

TY  - JOUR
ID  - 2496047
AU  - Jedličková, Adriena - Kristeková, Daniela - Husáková, Zuzana - Coufalík, Pavel - Vrlíková, Lucie - Smutná, Tereza - Capandová, Michaela - Alexa, Lukáš - Lusková, Denisa - Křůmal, Kamil - Jakešová, Veronika - Večeřa, Zbyněk - Zezula, Nikodém - Kanický, Viktor - Hampl, Aleš - Vaculovič, Tomáš - Mikuška, Pavel - Dumková, Jana - Buchtová, Marcela
PY  - 2025
TI  - Inhaled Lead Nanoparticles Enter the Brain through the Olfactory Pathway and Induce Neurodegenerative Changes Resembling Tauopathies
JF  - ACS Nano
VL  - 19
IS  - 13
SP  - 12799-12826
EP  - 12799-12826
PB  - American Chemical Society
SN  - 19360851
KW  - BBB
KW  - clearance ability
KW  - cytoskeleton
KW  - mTOR
KW  - nanotoxicity
KW  - neurodegeneration diseases
KW  - tau
UR  - https://pubs.acs.org/doi/10.1021/acsnano.4c14571
N2  - Lead nanoparticles (PbNPs) in air pollution pose a significant threat to human health, especially due to their neurotoxic effects. In this study, we exposed mice to lead(II) oxide nanoparticles (PbONPs) in inhalation chambers to mimic real-life exposure and assess their impact on the brain. PbONPs caused the formation of Hirano bodies and pathological changes related to neurodegenerative disorders through cytoskeletal disruptions without the induction of inflammation. Damage to astrocytic endfeet and capillary endothelial cells indicated a compromised blood-brain barrier (BBB), allowing PbONPs to enter the brain. Additionally, NPs were detected along the olfactory pathway, including fila olfactoria, suggesting that at least a proportion of PbNPs enter the brain directly by passing through the olfactory epithelium. PbNP inhalation severely damaged the apical parts of olfactory epithelial cells, including the loss of microtubules in their ciliary distal segments. Inhalation of PbONPs led to the rapid accumulation of lead in the brain, while more soluble lead(II) nitrate NPs did not accumulate significantly until 11 weeks of exposure. PbNPs induced disruption of the BBB at multiple levels, ranging from ultrastructural changes to functional impairments of the barrier; however, they did not induce systemic inflammation in the brain. The clearance ability of the brain to remove Pb was very low for both types of NPs, with significant pathological effects persisting even after a long clearance period. Cation-binding proteins (ZBTB20 and calbindin1) were distributed unevenly in the brain, with the strongest signal located in the hippocampus, which exhibited the greatest defects in nuclear architecture, indicating that this area is the most sensitive structure for PbNP exposure. PbNP exposure also altered the PI3K/Akt/mTOR signaling pathway, and tau phosphorylation in the hippocampus and inhibition of tau phosphorylation by GSK-3 inhibitor rescued the negative effect of PbONPs on the intracellular calcium level in trigeminal ganglion cultures. In zebrafish larvae, PbONPs affected locomotor activity and reduced calcium levels in the medium enhanced negative effect of PbONP on animal mobility, even increasing lethality. These findings suggest that cytoskeletal disruption and calcium dysregulation are key factors in PbNP-induced neurotoxicity, providing potential targets for therapeutic intervention to prevent neurodegenerative changes following PbNP exposure.
ER  -

JEDLIČKOVÁ, Adriena; Daniela KRISTEKOVÁ; Zuzana HUSÁKOVÁ; Pavel COUFALÍK; Lucie VRLÍKOVÁ; Tereza SMUTNÁ; Michaela CAPANDOVÁ; Lukáš ALEXA; Denisa LUSKOVÁ; Kamil KŘŮMAL; Veronika JAKEŠOVÁ; Zbyněk VEČEŘA; Nikodém ZEZULA; Viktor KANICKÝ; Aleš HAMPL; Tomáš VACULOVIČ; Pavel MIKUŠKA; Jana DUMKOVÁ a Marcela BUCHTOVÁ. Inhaled Lead Nanoparticles Enter the Brain through the Olfactory Pathway and Induce Neurodegenerative Changes Resembling Tauopathies. \textit{ACS Nano}. American Chemical Society, 2025, roč.~19, č.~13, s.~12799-12826. ISSN~1936-0851. Dostupné z: https://doi.org/10.1021/acsnano.4c14571.

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