Fu Yiming, Zheng Pengfang, She Xiaojun, Zhu Yingwen, Fu Bo, Ma Kefeng, Yang Honglian, Gao Xiujie, Cui Bo
Military Medical Sciences Academy, Tianjin, 300050, China.
Unit 92619 of the PLA, Hainan, 572001, China.
J Transl Med. 2025 Jun 2;23(1):613. doi: 10.1186/s12967-025-06501-7.
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.
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.
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.
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.
噪声暴露是一种与认知障碍相关的环境应激源。特定工作环境中的工人经常暴露于全天候噪声中，并经历与阿尔茨海默病类似的神经病理学相关的严重情绪和认知功能障碍。然而，其潜在的神经机制尚未得到广泛研究。
使用雄性Wistar大鼠评估全天候噪声暴露后认知障碍的分子途径。采用旷场试验和莫里斯水迷宫试验评估认知表现。利用RNA测序确定认知障碍的关键调节因子和病理途径。通过苏木精-伊红染色、尼氏染色、透射电子显微镜和免疫荧光观察组织学变化。进行蛋白质印迹法检测凋亡标志物的改变。
全天候噪声暴露显著诱导大鼠认知能力下降和神经元损伤。对对照大鼠和噪声暴露大鼠海马组织进行转录组测序发现，血清/糖皮质激素调节激酶1（SGK1）基因的表达降低，其蛋白质水平相应下降。此外，这种失调导致细胞内PI3K/SGK1/Foxo3途径受到抑制，引发凋亡蛋白Bcl-2、Bax、Fasl和TRAIL的上调。
这些发现表明，全天候噪声暴露诱导海马神经元凋亡，从而加剧认知障碍。这阐明了PI3K/SGK1/Foxo3途径在噪声诱导的神经元损伤中的潜在作用。
