BRAIN RESEARCH BULLETIN
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2022
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IF 3.715
Lin Bai,Yingying Wu,Ruike Wang,Rundong Liu,Mengchen Liu,Qiong Li,Yue Ba,Huizhen Zhang,Guoyu Zhou,Fangfang Yu,Hui Huang
As a ubiquitous toxic heavy metal, lead (Pb) exposure is known to be implicated in the onset and development of neurodegenerative diseases which may cause more serious health hazards with age and the accumulation of Pb in the body. Autophagy is the main degradation route for abnormal aggregated proteins and damaged cell organelles. Here, we aimed to study the effects of adolescent Pb exposure on autophagy at different life nodes. In this study, we developed a time-series model of Pb exposure in mice and randomly divided 4-week-old male C57BL/6 mice into six groups (4 C, 13 C, 16 C, 4Pb, 13Pb and 16Pb). Mice in Pb groups was consumed deionized water containing 0.2 % Pb(Ac) 2 for 3 months and then reared to anticipated life nodes, while the control group consumed deionized water. Western blot and Real-time qPCR were used to assess the effects of developmental Pb exposure on individual components of the autophagy machinery and modulation of microtubule-associated protein 1 light chain 3 (LC3) at each age stage. Our results showed that Pb exposure during adolescence reduced the p-mTOR/mTOR ratios with enhanced expression of Beclin-1, Atg12 and Atg7in both the hippocampus (HPC) and prefrontal cortex (PFC) of senescent mice while upregulation of LC3II/LC3I ratios and p62 suggested that autophagy mediates degradation was interrupted. Overall, we confirm that Pb exposure during adolescence promotes autophagic processes in the aged mice brain and that autophagic degradation is hindered, ultimately leading to a failure of autophagic degradation.
研究领域:
毒理学
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神经科学
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分子生物学
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发育生物学
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衰老研究
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
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2024
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IF 2.2
Jingzhi WANG,Zhongyu HUANG,Yiwen LI,Qian LI,Xi LI,Li CHEN
At present, there lacks a definitive pharmaceutical intervention or therapeutic approach for diabetes-associated cognitive impairment. Herein, we delved into the impact of electroacupuncture on cognitive function in high-fat diet/streptozocin (HFD/STZ)-induced T2DM mice and underlying mechanisms. Hippocampal insulin resistance was determined by western blot analysis. Cognitive function was evaluated by Morris water maze test. The morphology of the hippocampal neurons was observed through hematoxylin & eosin staining and Nissl staining. Synaptic plasticity was assessed by western blot analysis. Immunofluorescence, immunohistochemistry, western blot and real-time PCR were employed to detect the levels of ferroptosis markers, autophagy markers, and netrin-1. Electroacupuncture treatment exhibited ameliorative outcomes on spatial learning, memory function, hippocampal insulin resistance, neuronal damage, and synaptic plasticity in T2DM mice. Furthermore, it effectively suppressed neuronal ferroptosis within the hippocampus by upregulating GPX4 and SLC7A11 expression, and reducing 4-HNE expression. Meanwhile, electroacupuncture intervention increased the levels of Beclin1 and LC3II/LC3I, as well as decreased the levels of p62 and phosphorylated-mTOR in the hippocampus of T2DM mice, suggesting that electroacupuncture facilitated autophagy activation by inhibiting mTOR activity. 3-MA-mediated autophagy inhibition undermined the beneficial effects of electroacupuncture on neuronal ferroptosis and cognitive deficits in T2DM mice. Additionally, the beneficial effects of electroacupuncture on autophagy and ferroptosis was achieved by upregulation of netrin-1 in the hippocampus. Our study revealed that that electroacupuncture therapy inhibited neuronal ferroptosis via the activation of autophagy, thereby ameliorating cognitive deficits in T2DM mice.
研究领域:
神经科学
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糖尿病学
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认知科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOLOGY REPORTS
·
2024
·Vol. 51
·期 1
·1-10
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IF 2.6
Li Zhipeng,Jiao Yang,Wu Zhisong,Liu Haoge,Li Yang,Cai Yaodong,Wei Wan,Cao Fang
Background Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by a constant incidence rate. Unfortunately, effective pharmacological treatments for this condition are lacking and the identification of novel therapeutic approaches and underlying pathological mechanisms are required. This study investigated the potential of quercetin in alleviating pulmonary fibrosis by promoting autophagy and activation of the SIRT1/AMPK pathway. Methods Mouse models of IPF were divided into four treatment groups: control, bleomycin (BLM), quercetin (Q), and quercetin + EX-527 (Q + E) treatment. Pulmonary fibrosis was induced in the mouse models through intratracheal instillation of BLM. Various indexes were identified through histological staining, Western blotting analysis, enzyme-linked immunosorbent assay, immunohistochemistry, and transmission electron microscopy. Results Quercetin treatment ameliorated the pathology of BLM-induced pulmonary fibrosis of mice by reducing α-smooth muscle actin (α-SMA), collagen I (Col I), and collagen III (Col III) levels, and also improved the level of E-cadherin in lung tissue. Furthermore, Quercetin significantly enhanced LC3II/LC3I levels, decreased P62 expression, and increased the number of autophagosomes in lung tissue. These effects were accompanied by the activation of the SIRT1/AMPK pathway. Treatment with EX-527, an inhibitor for SIRT1, reversed all effects induced by quercetin. Conclusion This study showed that quercetin could alleviate pulmonary fibrosis and improve epithelial-mesenchymal transition by acting on the SIRT1/AMPK signaling pathway, which may be achieved by regulating the level of autophagy.
研究领域:
药理学
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病理学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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