miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the Brain
Cigarettes contain various chemicals that cause damage to nerve cells. Exposure to cigarette smoke (CS) causes insulin resistance (IR) in nerve cells. However, the mechanisms for a disorder in the cigarette-induced insulin signaling pathway and in neurotoxicity remain unclear. Therefore, we evaluate...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/11/12/969 |
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| author | Qian Sun Hailan Wang Mingxue Yang Haibo Xia Yao Wu Qizhan Liu Huanwen Tang |
| author_facet | Qian Sun Hailan Wang Mingxue Yang Haibo Xia Yao Wu Qizhan Liu Huanwen Tang |
| author_sort | Qian Sun |
| collection | DOAJ |
| description | Cigarettes contain various chemicals that cause damage to nerve cells. Exposure to cigarette smoke (CS) causes insulin resistance (IR) in nerve cells. However, the mechanisms for a disorder in the cigarette-induced insulin signaling pathway and in neurotoxicity remain unclear. Therefore, we evaluated, by a series of pathology analyses and behavioral tests, the neurotoxic effects of chronic exposure to CS on C57BL/6 mice. Mice exposed to CS with more than 200 mg/m<sup>3</sup> total particulate matter (TPM) exhibited memory deficits and cognitive impairment. Pathological staining of paraffin sections of mouse brain tissue revealed that CS-exposed mice had, in the brain, neuronal damage characterized by thinner pyramidal and granular cell layers and fewer neurons. Further, the exposure of SH-SY5Y cells to cigarette smoke extract (CSE) resulted in diminished insulin sensitivity and reduced glucose uptake in a dose-dependent fashion. The PI3K/GSK3 insulin signaling pathway is particularly relevant to neurotoxicity. microRNAs are involved in the PI3K/GSK3β/p-Tau pathway, and we found that cigarette exposure activates miR-153-3p, decreases PI3K regulatory subunits PIK3R1, and induces Tau hyperphosphorylation. Exposure to an miR-153 inhibitor or to a PI3K inhibitor alleviated the reduced insulin sensitivity caused by CS. Therefore, our results indicate that miR-153-3p, via PIK3R1, causes insulin resistance in the brain, and is involved in CS-induced neurotoxicity. |
| first_indexed | 2024-03-08T20:18:47Z |
| format | Article |
| id | doaj.art-1132bc6fb9a744d6a278746676890974 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-08T20:18:47Z |
| publishDate | 2023-11-01 |
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| record_format | Article |
| series | Toxics |
| spelling | doaj.art-1132bc6fb9a744d6a2787466768909742023-12-22T14:46:00ZengMDPI AGToxics2305-63042023-11-01111296910.3390/toxics11120969miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the BrainQian Sun0Hailan Wang1Mingxue Yang2Haibo Xia3Yao Wu4Qizhan Liu5Huanwen Tang6Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, ChinaCenter for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, ChinaCenter for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, ChinaCenter for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, ChinaCigarettes contain various chemicals that cause damage to nerve cells. Exposure to cigarette smoke (CS) causes insulin resistance (IR) in nerve cells. However, the mechanisms for a disorder in the cigarette-induced insulin signaling pathway and in neurotoxicity remain unclear. Therefore, we evaluated, by a series of pathology analyses and behavioral tests, the neurotoxic effects of chronic exposure to CS on C57BL/6 mice. Mice exposed to CS with more than 200 mg/m<sup>3</sup> total particulate matter (TPM) exhibited memory deficits and cognitive impairment. Pathological staining of paraffin sections of mouse brain tissue revealed that CS-exposed mice had, in the brain, neuronal damage characterized by thinner pyramidal and granular cell layers and fewer neurons. Further, the exposure of SH-SY5Y cells to cigarette smoke extract (CSE) resulted in diminished insulin sensitivity and reduced glucose uptake in a dose-dependent fashion. The PI3K/GSK3 insulin signaling pathway is particularly relevant to neurotoxicity. microRNAs are involved in the PI3K/GSK3β/p-Tau pathway, and we found that cigarette exposure activates miR-153-3p, decreases PI3K regulatory subunits PIK3R1, and induces Tau hyperphosphorylation. Exposure to an miR-153 inhibitor or to a PI3K inhibitor alleviated the reduced insulin sensitivity caused by CS. Therefore, our results indicate that miR-153-3p, via PIK3R1, causes insulin resistance in the brain, and is involved in CS-induced neurotoxicity.https://www.mdpi.com/2305-6304/11/12/969cigaretteneurotoxicityinsulin resistancemiR-153 |
| spellingShingle | Qian Sun Hailan Wang Mingxue Yang Haibo Xia Yao Wu Qizhan Liu Huanwen Tang miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the Brain Toxics cigarette neurotoxicity insulin resistance miR-153 |
| title | miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the Brain |
| title_full | miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the Brain |
| title_fullStr | miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the Brain |
| title_full_unstemmed | miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the Brain |
| title_short | miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the Brain |
| title_sort | mir 153 3p via pik3r1 is involved in cigarette smoke induced neurotoxicity in the brain |
| topic | cigarette neurotoxicity insulin resistance miR-153 |
| url | https://www.mdpi.com/2305-6304/11/12/969 |
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