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miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the Brain.
- Source :
- Toxics; Dec2023, Vol. 11 Issue 12, p969, 16p
- Publication Year :
- 2023
-
Abstract
- 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<superscript>3</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 23056304
- Volume :
- 11
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Toxics
- Publication Type :
- Academic Journal
- Accession number :
- 174494059
- Full Text :
- https://doi.org/10.3390/toxics11120969