Role of BDNF-TrkB signaling pathway in early-life cadmium exposure induced cognitive dysfunction in mice
BackgroundWith the rapid industrialization, cadmium has become a primary heavy metal pollutant in cultivated land soil in China, which seriously affects human health. Previous studies have found that cadmium exposure associates with cognitive dysfunction in individuals, but there is a lack of resear...
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Editorial Committee of Journal of Environmental and Occupational Medicine
2024-11-01
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| Series: | 环境与职业医学 |
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| Online Access: | http://www.jeom.org/article/cn/10.11836/JEOM24045 |
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| author | Yan SHI Siqi YANG Yougang WANG Qiumei WU Jinquan LI |
| author_facet | Yan SHI Siqi YANG Yougang WANG Qiumei WU Jinquan LI |
| author_sort | Yan SHI |
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| description | BackgroundWith the rapid industrialization, cadmium has become a primary heavy metal pollutant in cultivated land soil in China, which seriously affects human health. Previous studies have found that cadmium exposure associates with cognitive dysfunction in individuals, but there is a lack of research on the mechanism of cadmium exposure associated cognitive impairment in offspring in early life which is more vulnerable to various toxins and crucial for development of the neuro.ObjectiveTo explore the potential mechanism of brain-derived neurotrophic factor/tyrosine kinase receptor B (BDNF-TrkB) signaling pathway in cognitive dysfunction in mice after cadmium exposure in early-life.MethodsTwelve 8-week-old C57BL/6 pregnant mice were randomly divided into 2 groups, namely control group and cadmium exposure group, with 6 mice in each group. The exposure period was from pregnancy day 4.5 to lactation day 21 (E4.5-P21), during which distilled water or cadmium chloride solution (2.5 mg·kg−1·d−1) was given. After lactation, the offspring of the control group and the cadmium exposure group were given distilled water until 8 weeks of age. Then the toxicity effects of cadmium exposure on mice were evaluated by body weight and selected biochemical indicators. The cadmium content in brain was detected and the learning and memory ability was tested by Y maze and Morris water maze to evaluate cognitive function of offspring mice. Histopathological changes of the hippocampus were observed after Nissl staining and Golgi staining. The mRNA and protein expression levels of the BDNF-TrkB pathway and synapse were detected by real-time quantitative PCR (qPCR) and Western blot.ResultsCompared with the control group, no significant change was found in body weight, liver or kidney function in the cadmium exposure group (P> 0.05). However, compared with the control group, the cadmium content in brain was increased in the cadmium exposure group (P<0.001). The behavioral changes associated with cognitive dysfunction were positive in the cadmium exposure group (all P<0.05). The histopathological observation after Nissl staining showed abnormal tissue structure, decreased number of neurons and increased karyopyknosis in the cadmium exposure group (P<0.01).The spine density of Golgi staining was decreased in the cadmium exposure group (P<0.001). The BDNF-TrkB pathway-related mRNA and the synapse-related mRNA in the hippocampus were reduced in the cadmium exposure group (all P<0.05). The expression levels of BDNF-TrkB pathway-related proteins and synapse-related proteins in the hippocampus were also reduced in the cadmium exposure group (P<0.05).ConclusionEarly-life cadmium exposure may induce synaptic dysplasia and lead to cognitive dysfunction by down-regulating the BDNF-TrkB signaling pathway in mice. |
| format | Article |
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| issn | 2095-9982 |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-94c2a17348df43aaa3c6fa5a92a285ec2025-08-20T02:31:08ZengEditorial Committee of Journal of Environmental and Occupational Medicine环境与职业医学2095-99822024-11-0141111283128910.11836/JEOM2404524045Role of BDNF-TrkB signaling pathway in early-life cadmium exposure induced cognitive dysfunction in miceYan SHI0Siqi YANG1Yougang WANG2Qiumei WU3Jinquan LI4Brain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, ChinaBrain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, ChinaBrain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, ChinaBrain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, ChinaBrain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, ChinaBackgroundWith the rapid industrialization, cadmium has become a primary heavy metal pollutant in cultivated land soil in China, which seriously affects human health. Previous studies have found that cadmium exposure associates with cognitive dysfunction in individuals, but there is a lack of research on the mechanism of cadmium exposure associated cognitive impairment in offspring in early life which is more vulnerable to various toxins and crucial for development of the neuro.ObjectiveTo explore the potential mechanism of brain-derived neurotrophic factor/tyrosine kinase receptor B (BDNF-TrkB) signaling pathway in cognitive dysfunction in mice after cadmium exposure in early-life.MethodsTwelve 8-week-old C57BL/6 pregnant mice were randomly divided into 2 groups, namely control group and cadmium exposure group, with 6 mice in each group. The exposure period was from pregnancy day 4.5 to lactation day 21 (E4.5-P21), during which distilled water or cadmium chloride solution (2.5 mg·kg−1·d−1) was given. After lactation, the offspring of the control group and the cadmium exposure group were given distilled water until 8 weeks of age. Then the toxicity effects of cadmium exposure on mice were evaluated by body weight and selected biochemical indicators. The cadmium content in brain was detected and the learning and memory ability was tested by Y maze and Morris water maze to evaluate cognitive function of offspring mice. Histopathological changes of the hippocampus were observed after Nissl staining and Golgi staining. The mRNA and protein expression levels of the BDNF-TrkB pathway and synapse were detected by real-time quantitative PCR (qPCR) and Western blot.ResultsCompared with the control group, no significant change was found in body weight, liver or kidney function in the cadmium exposure group (P> 0.05). However, compared with the control group, the cadmium content in brain was increased in the cadmium exposure group (P<0.001). The behavioral changes associated with cognitive dysfunction were positive in the cadmium exposure group (all P<0.05). The histopathological observation after Nissl staining showed abnormal tissue structure, decreased number of neurons and increased karyopyknosis in the cadmium exposure group (P<0.01).The spine density of Golgi staining was decreased in the cadmium exposure group (P<0.001). The BDNF-TrkB pathway-related mRNA and the synapse-related mRNA in the hippocampus were reduced in the cadmium exposure group (all P<0.05). The expression levels of BDNF-TrkB pathway-related proteins and synapse-related proteins in the hippocampus were also reduced in the cadmium exposure group (P<0.05).ConclusionEarly-life cadmium exposure may induce synaptic dysplasia and lead to cognitive dysfunction by down-regulating the BDNF-TrkB signaling pathway in mice.http://www.jeom.org/article/cn/10.11836/JEOM24045early lifecadmiumbrain-derived neurotrophic factor/tyrosine kinase receptor bsynapsecognitive dysfunction |
| spellingShingle | Yan SHI Siqi YANG Yougang WANG Qiumei WU Jinquan LI Role of BDNF-TrkB signaling pathway in early-life cadmium exposure induced cognitive dysfunction in mice 环境与职业医学 early life cadmium brain-derived neurotrophic factor/tyrosine kinase receptor b synapse cognitive dysfunction |
| title | Role of BDNF-TrkB signaling pathway in early-life cadmium exposure induced cognitive dysfunction in mice |
| title_full | Role of BDNF-TrkB signaling pathway in early-life cadmium exposure induced cognitive dysfunction in mice |
| title_fullStr | Role of BDNF-TrkB signaling pathway in early-life cadmium exposure induced cognitive dysfunction in mice |
| title_full_unstemmed | Role of BDNF-TrkB signaling pathway in early-life cadmium exposure induced cognitive dysfunction in mice |
| title_short | Role of BDNF-TrkB signaling pathway in early-life cadmium exposure induced cognitive dysfunction in mice |
| title_sort | role of bdnf trkb signaling pathway in early life cadmium exposure induced cognitive dysfunction in mice |
| topic | early life cadmium brain-derived neurotrophic factor/tyrosine kinase receptor b synapse cognitive dysfunction |
| url | http://www.jeom.org/article/cn/10.11836/JEOM24045 |
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