Around-the-clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the PI3K/SGK1/Foxo3 signaling pathway

Abstract Background Noise exposure is an environmental stressor associated with cognitive impairment. Workers in specific work environments are often exposed to around-the-clock noise and experience severe emotional and cognitive dysfunctions associated with neuropathology similar to Alzheimer’s dis...

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Main Authors: Yiming Fu, Pengfang Zheng, Xiaojun She, Yingwen Zhu, Bo Fu, Kefeng Ma, Honglian Yang, Xiujie Gao, Bo Cui
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-025-06501-7
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author Yiming Fu
Pengfang Zheng
Xiaojun She
Yingwen Zhu
Bo Fu
Kefeng Ma
Honglian Yang
Xiujie Gao
Bo Cui
author_facet Yiming Fu
Pengfang Zheng
Xiaojun She
Yingwen Zhu
Bo Fu
Kefeng Ma
Honglian Yang
Xiujie Gao
Bo Cui
author_sort Yiming Fu
collection DOAJ
description Abstract Background Noise exposure is an environmental stressor associated with cognitive impairment. Workers in specific work environments are often exposed to around-the-clock noise and experience severe emotional and cognitive dysfunctions associated with neuropathology similar to Alzheimer’s disease. However, the underlying neural mechanisms have not been extensively investigated. Methods The molecular pathways underlying cognitive impairment following around-the-clock noise exposure were evaluated using male Wistar rats. The open-field and Morris water maze tests were used to assess cognitive performance. RNA sequencing was employed to identify key regulators and pathological pathways of cognitive impairment. Histological changes were observed using hematoxylin and eosin staining, Nissl staining, transmission electron microscopy, and immunofluorescence. Western blotting was performed to detect altered apoptotic markers. Results Around-the-clock noise exposure significantly induced cognitive decline and neuronal damage in rat. Transcriptome sequencing of hippocampal tissues from control and noise-exposed rats revealed that the expression of the serum/glucocorticoid regulated kinase 1 (SGK1) gene was reduced, with a corresponding decrease in its protein levels. Moreover, this dysregulation led to the inhibition of the intracellular PI3K/SGK1/Foxo3 pathway, triggering the upregulation of the apoptotic proteins Bcl-2, Bax, Fasl, and TRAIL. Conclusions These findings suggest that around-the-clock noise exposure induces hippocampal neuronal apoptosis, thus exacerbating cognitive impairment. This elucidates the potential role of the PI3K/SGK1/Foxo3 pathway in noise-induced neuronal damage.
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spelling doaj-art-19ce4f26478f4ff98367e9dc4667337c2025-08-20T02:05:14ZengBMCJournal of Translational Medicine1479-58762025-06-0123111310.1186/s12967-025-06501-7Around-the-clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the PI3K/SGK1/Foxo3 signaling pathwayYiming Fu0Pengfang Zheng1Xiaojun She2Yingwen Zhu3Bo Fu4Kefeng Ma5Honglian Yang6Xiujie Gao7Bo Cui8Military Medical Sciences AcademyMilitary Medical Sciences AcademyMilitary Medical Sciences AcademyMilitary Medical Sciences AcademyMilitary Medical Sciences AcademyMilitary Medical Sciences AcademyMilitary Medical Sciences AcademyMilitary Medical Sciences AcademyMilitary Medical Sciences AcademyAbstract Background Noise exposure is an environmental stressor associated with cognitive impairment. Workers in specific work environments are often exposed to around-the-clock noise and experience severe emotional and cognitive dysfunctions associated with neuropathology similar to Alzheimer’s disease. However, the underlying neural mechanisms have not been extensively investigated. Methods The molecular pathways underlying cognitive impairment following around-the-clock noise exposure were evaluated using male Wistar rats. The open-field and Morris water maze tests were used to assess cognitive performance. RNA sequencing was employed to identify key regulators and pathological pathways of cognitive impairment. Histological changes were observed using hematoxylin and eosin staining, Nissl staining, transmission electron microscopy, and immunofluorescence. Western blotting was performed to detect altered apoptotic markers. Results Around-the-clock noise exposure significantly induced cognitive decline and neuronal damage in rat. Transcriptome sequencing of hippocampal tissues from control and noise-exposed rats revealed that the expression of the serum/glucocorticoid regulated kinase 1 (SGK1) gene was reduced, with a corresponding decrease in its protein levels. Moreover, this dysregulation led to the inhibition of the intracellular PI3K/SGK1/Foxo3 pathway, triggering the upregulation of the apoptotic proteins Bcl-2, Bax, Fasl, and TRAIL. Conclusions These findings suggest that around-the-clock noise exposure induces hippocampal neuronal apoptosis, thus exacerbating cognitive impairment. This elucidates the potential role of the PI3K/SGK1/Foxo3 pathway in noise-induced neuronal damage.https://doi.org/10.1186/s12967-025-06501-7Around-the-clock noiseApoptosisCognitive impairmentSerum/glucocorticoid regulated kinase 1
spellingShingle Yiming Fu
Pengfang Zheng
Xiaojun She
Yingwen Zhu
Bo Fu
Kefeng Ma
Honglian Yang
Xiujie Gao
Bo Cui
Around-the-clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the PI3K/SGK1/Foxo3 signaling pathway
Journal of Translational Medicine
Around-the-clock noise
Apoptosis
Cognitive impairment
Serum/glucocorticoid regulated kinase 1
title Around-the-clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the PI3K/SGK1/Foxo3 signaling pathway
title_full Around-the-clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the PI3K/SGK1/Foxo3 signaling pathway
title_fullStr Around-the-clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the PI3K/SGK1/Foxo3 signaling pathway
title_full_unstemmed Around-the-clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the PI3K/SGK1/Foxo3 signaling pathway
title_short Around-the-clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the PI3K/SGK1/Foxo3 signaling pathway
title_sort around the clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the pi3k sgk1 foxo3 signaling pathway
topic Around-the-clock noise
Apoptosis
Cognitive impairment
Serum/glucocorticoid regulated kinase 1
url https://doi.org/10.1186/s12967-025-06501-7
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