Endoplasmic Reticulum Stress Underlies Nanosilver-Induced Neurotoxicity in Immature Rat Brain
The growing production of silver nanoparticles (AgNPs), and their widespread use in medical and consumer products, poses a potential threat to the environment and raises questions about biosafety. Immature organisms are particularly susceptible to various insults during development. The biological c...
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/13013 |
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| author | Beata Dąbrowska-Bouta Grzegorz Sulkowski Magdalena Gewartowska Lidia Strużyńska |
| author_facet | Beata Dąbrowska-Bouta Grzegorz Sulkowski Magdalena Gewartowska Lidia Strużyńska |
| author_sort | Beata Dąbrowska-Bouta |
| collection | DOAJ |
| description | The growing production of silver nanoparticles (AgNPs), and their widespread use in medical and consumer products, poses a potential threat to the environment and raises questions about biosafety. Immature organisms are particularly susceptible to various insults during development. The biological characteristics of immature organisms are different from those of adults, and dictate the consequences of exposure to various toxic substances, including AgNPs. Nanoparticles are highly reactive and can easily cross the blood–brain barrier (BBB) to accumulate in brain tissues. It is therefore important to investigate the molecular mechanisms of AgNP-induced neurotoxicity in the developing brain. Immature 2-week-old rats were exposed to a low dose of AgNPs (0.2 mg/kg b.w.) over a long period. Subsequently, brain tissues of the animals were subjected to ultrastructural and molecular analyses to determine endoplasmic reticulum (ER) stress. Ultrastructural markers of ER stress, such as pathological alterations in the ER and elongated forms of mitochondria accompanied by autophagy structures, were confirmed to be present in AgNP-exposed rat brain. Evidence for induction of ER stress in neurons was also provided by molecular markers. Upregulation of genes related to the ER-stress-induced unfolded protein response (UPR) pathway, such as GRP78, PERK, and CHOP ATF-6, was observed at the transcriptional and translational levels. The results show that prolonged exposure of immature rats to a low dose of AgNPs during the developmental period leads to induction of ER stress in the neurons of the developing brain. Simultaneously, in response to AgNP-induced ER stress, neurons promote protective mechanisms that partially compensate for ER stress by regulating the biodynamic processes of mitochondria and autophagy. |
| first_indexed | 2024-03-09T19:01:52Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:01:52Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b79888f577a0480f8fac288230b9cff92023-11-24T05:00:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211301310.3390/ijms232113013Endoplasmic Reticulum Stress Underlies Nanosilver-Induced Neurotoxicity in Immature Rat BrainBeata Dąbrowska-Bouta0Grzegorz Sulkowski1Magdalena Gewartowska2Lidia Strużyńska3Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, PolandLaboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, PolandElectron Microscopy Research Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, PolandLaboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, PolandThe growing production of silver nanoparticles (AgNPs), and their widespread use in medical and consumer products, poses a potential threat to the environment and raises questions about biosafety. Immature organisms are particularly susceptible to various insults during development. The biological characteristics of immature organisms are different from those of adults, and dictate the consequences of exposure to various toxic substances, including AgNPs. Nanoparticles are highly reactive and can easily cross the blood–brain barrier (BBB) to accumulate in brain tissues. It is therefore important to investigate the molecular mechanisms of AgNP-induced neurotoxicity in the developing brain. Immature 2-week-old rats were exposed to a low dose of AgNPs (0.2 mg/kg b.w.) over a long period. Subsequently, brain tissues of the animals were subjected to ultrastructural and molecular analyses to determine endoplasmic reticulum (ER) stress. Ultrastructural markers of ER stress, such as pathological alterations in the ER and elongated forms of mitochondria accompanied by autophagy structures, were confirmed to be present in AgNP-exposed rat brain. Evidence for induction of ER stress in neurons was also provided by molecular markers. Upregulation of genes related to the ER-stress-induced unfolded protein response (UPR) pathway, such as GRP78, PERK, and CHOP ATF-6, was observed at the transcriptional and translational levels. The results show that prolonged exposure of immature rats to a low dose of AgNPs during the developmental period leads to induction of ER stress in the neurons of the developing brain. Simultaneously, in response to AgNP-induced ER stress, neurons promote protective mechanisms that partially compensate for ER stress by regulating the biodynamic processes of mitochondria and autophagy.https://www.mdpi.com/1422-0067/23/21/13013AgNPsER stressdevelopmental neurotoxicityunfolded protein responseUPR pathway |
| spellingShingle | Beata Dąbrowska-Bouta Grzegorz Sulkowski Magdalena Gewartowska Lidia Strużyńska Endoplasmic Reticulum Stress Underlies Nanosilver-Induced Neurotoxicity in Immature Rat Brain International Journal of Molecular Sciences AgNPs ER stress developmental neurotoxicity unfolded protein response UPR pathway |
| title | Endoplasmic Reticulum Stress Underlies Nanosilver-Induced Neurotoxicity in Immature Rat Brain |
| title_full | Endoplasmic Reticulum Stress Underlies Nanosilver-Induced Neurotoxicity in Immature Rat Brain |
| title_fullStr | Endoplasmic Reticulum Stress Underlies Nanosilver-Induced Neurotoxicity in Immature Rat Brain |
| title_full_unstemmed | Endoplasmic Reticulum Stress Underlies Nanosilver-Induced Neurotoxicity in Immature Rat Brain |
| title_short | Endoplasmic Reticulum Stress Underlies Nanosilver-Induced Neurotoxicity in Immature Rat Brain |
| title_sort | endoplasmic reticulum stress underlies nanosilver induced neurotoxicity in immature rat brain |
| topic | AgNPs ER stress developmental neurotoxicity unfolded protein response UPR pathway |
| url | https://www.mdpi.com/1422-0067/23/21/13013 |
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