Lead-induced hypertension and cognitive dysfunction: brain amyloid pathology
Abstract Background Lead (Pb) exposure is a recognized environmental risk factor for cognitive decline and may aggravate Alzheimer's disease (AD) pathology through hypertension-related mechanisms. However, the specific role of mineralocorticoid receptor (MR) signaling in this process remains un...
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| Format: | Article |
| Language: | English |
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BMC
2025-08-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02965-x |
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| author | Yunbo Zhang Yao Xu Yanling Song Yachun Wang Minghui Chen Xinbo Ji Yunyun Lin Shenhong Gu |
| author_facet | Yunbo Zhang Yao Xu Yanling Song Yachun Wang Minghui Chen Xinbo Ji Yunyun Lin Shenhong Gu |
| author_sort | Yunbo Zhang |
| collection | DOAJ |
| description | Abstract Background Lead (Pb) exposure is a recognized environmental risk factor for cognitive decline and may aggravate Alzheimer's disease (AD) pathology through hypertension-related mechanisms. However, the specific role of mineralocorticoid receptor (MR) signaling in this process remains unclear. Objectives This study investigated whether Pb-induced hypertension exacerbates amyloid pathology via MR activation, and evaluated the therapeutic effects of amlodipine and spironolactone in an AD mouse model. Methods APPSwDI transgenic mice were exposed to Pb acetate (25 mg/kg/day) for 8 weeks, with or without concurrent treatment with amlodipine or spironolactone. Cognitive behavior, blood pressure, renal function, neuroinflammation, oxidative stress, and brain amyloid deposition were assessed. Results Pb exposure significantly increased systolic blood pressure, impaired cognition, elevated IL-1β and IL-6 levels, and enhanced brain amyloid burden. MR expression in brain tissue was upregulated following Pb exposure. Both spironolactone and amlodipine improved cognitive performance and reduced neuroinflammation and oxidative stress. Spironolactone more effectively suppressed MR expression and amyloid deposition, though some group differences did not reach statistical significance. Conclusions Pb exacerbates AD-like pathology through MR-related hypertensive and inflammatory mechanisms. MR antagonism by spironolactone offers greater neuroprotection than calcium channel blockade in this context. These findings suggest that targeting MR signaling may be a promising therapeutic strategy for environmentally induced AD risk. Graphical Abstract |
| format | Article |
| id | doaj-art-21bf4ff859d84c78b31c93a3e50e0f77 |
| institution | DOAJ |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-21bf4ff859d84c78b31c93a3e50e0f772025-08-20T03:04:26ZengBMCEuropean Journal of Medical Research2047-783X2025-08-0130111410.1186/s40001-025-02965-xLead-induced hypertension and cognitive dysfunction: brain amyloid pathologyYunbo Zhang0Yao Xu1Yanling Song2Yachun Wang3Minghui Chen4Xinbo Ji5Yunyun Lin6Shenhong Gu7Department of General Practice, The First Affiliated Hospital of Hainan Medical UniversityHainan Medical UniversityDepartment of General Practice, The First Affiliated Hospital of Hainan Medical UniversityDepartment of General Practice, The First Affiliated Hospital of Hainan Medical UniversityDepartment of General Practice, The First Affiliated Hospital of Hainan Medical UniversityDepartment of General Practice, The First Affiliated Hospital of Hainan Medical UniversityDepartment of General Practice, The First Affiliated Hospital of Hainan Medical UniversityDepartment of General Practice, The First Affiliated Hospital of Hainan Medical UniversityAbstract Background Lead (Pb) exposure is a recognized environmental risk factor for cognitive decline and may aggravate Alzheimer's disease (AD) pathology through hypertension-related mechanisms. However, the specific role of mineralocorticoid receptor (MR) signaling in this process remains unclear. Objectives This study investigated whether Pb-induced hypertension exacerbates amyloid pathology via MR activation, and evaluated the therapeutic effects of amlodipine and spironolactone in an AD mouse model. Methods APPSwDI transgenic mice were exposed to Pb acetate (25 mg/kg/day) for 8 weeks, with or without concurrent treatment with amlodipine or spironolactone. Cognitive behavior, blood pressure, renal function, neuroinflammation, oxidative stress, and brain amyloid deposition were assessed. Results Pb exposure significantly increased systolic blood pressure, impaired cognition, elevated IL-1β and IL-6 levels, and enhanced brain amyloid burden. MR expression in brain tissue was upregulated following Pb exposure. Both spironolactone and amlodipine improved cognitive performance and reduced neuroinflammation and oxidative stress. Spironolactone more effectively suppressed MR expression and amyloid deposition, though some group differences did not reach statistical significance. Conclusions Pb exacerbates AD-like pathology through MR-related hypertensive and inflammatory mechanisms. MR antagonism by spironolactone offers greater neuroprotection than calcium channel blockade in this context. These findings suggest that targeting MR signaling may be a promising therapeutic strategy for environmentally induced AD risk. Graphical Abstracthttps://doi.org/10.1186/s40001-025-02965-xAlzheimer’s diseasePbCognitive impairmentNeuroinflammationAmyloid plaqueAmlodipine |
| spellingShingle | Yunbo Zhang Yao Xu Yanling Song Yachun Wang Minghui Chen Xinbo Ji Yunyun Lin Shenhong Gu Lead-induced hypertension and cognitive dysfunction: brain amyloid pathology European Journal of Medical Research Alzheimer’s disease Pb Cognitive impairment Neuroinflammation Amyloid plaque Amlodipine |
| title | Lead-induced hypertension and cognitive dysfunction: brain amyloid pathology |
| title_full | Lead-induced hypertension and cognitive dysfunction: brain amyloid pathology |
| title_fullStr | Lead-induced hypertension and cognitive dysfunction: brain amyloid pathology |
| title_full_unstemmed | Lead-induced hypertension and cognitive dysfunction: brain amyloid pathology |
| title_short | Lead-induced hypertension and cognitive dysfunction: brain amyloid pathology |
| title_sort | lead induced hypertension and cognitive dysfunction brain amyloid pathology |
| topic | Alzheimer’s disease Pb Cognitive impairment Neuroinflammation Amyloid plaque Amlodipine |
| url | https://doi.org/10.1186/s40001-025-02965-x |
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