Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia
Abstract Lactation is a crucial phase of brain development, and the events and nutrients during this period have long-term consequences for the occurrence of depression. This study investigated the effect and mechanism of lactoferrin (LF) deficiency during lactation on depression in adulthood. Lacta...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01094-9 |
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| author | Wenli Wang Qin An Yunxia Zou Yunping Dai Qingyong Meng Yali Zhang |
| author_facet | Wenli Wang Qin An Yunxia Zou Yunping Dai Qingyong Meng Yali Zhang |
| author_sort | Wenli Wang |
| collection | DOAJ |
| description | Abstract Lactation is a crucial phase of brain development, and the events and nutrients during this period have long-term consequences for the occurrence of depression. This study investigated the effect and mechanism of lactoferrin (LF) deficiency during lactation on depression in adulthood. Lactation LF-deficient mice were established by nursing wild-type mice using LF systemic knockout mother mice. Additionally, 14-day-old mice were injected with lipopolysaccharide (LPS) and subjected to chronic unpredictable mild stress when they reached 6 weeks of age. The results show that lactation lactoferrin deficiency increases depression-like behavior in adult mice, and the mechanism is associated with heightened neuronal damage, abnormal microglial activation, and decreased BDNF in the hippocampus. In contrast, recombinant human lactoferrin promotes neuronal proliferation by upregulating ERK 1 and 2 phosphorylation and attenuates LPS-induced neuronal injury and microglial activation by inhibiting the activation of Toll-like receptor 4—nuclear factor-kappa B pathway in vitro. Our findings suggest that lactoferrin intake during lactation protects neurons by regulating microglial activation, thereby effectively reducing depressive symptoms in adults. |
| format | Article |
| id | doaj-art-18ee0795258f4e9287c9dd2df58248c4 |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-18ee0795258f4e9287c9dd2df58248c42025-02-09T12:42:06ZengBMCMolecular Medicine1528-36582025-02-0131112010.1186/s10020-025-01094-9Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microgliaWenli Wang0Qin An1Yunxia Zou2Yunping Dai3Qingyong Meng4Yali Zhang5College of Food Science and Nutritional Engineering, China Agricultural UniversityCollege of Food Science and Nutritional Engineering, China Agricultural UniversityCollege of Food Science and Nutritional Engineering, China Agricultural UniversityCollege of Biological Sciences, China Agricultural UniversityCollege of Biological Sciences, China Agricultural UniversityCollege of Food Science and Nutritional Engineering, China Agricultural UniversityAbstract Lactation is a crucial phase of brain development, and the events and nutrients during this period have long-term consequences for the occurrence of depression. This study investigated the effect and mechanism of lactoferrin (LF) deficiency during lactation on depression in adulthood. Lactation LF-deficient mice were established by nursing wild-type mice using LF systemic knockout mother mice. Additionally, 14-day-old mice were injected with lipopolysaccharide (LPS) and subjected to chronic unpredictable mild stress when they reached 6 weeks of age. The results show that lactation lactoferrin deficiency increases depression-like behavior in adult mice, and the mechanism is associated with heightened neuronal damage, abnormal microglial activation, and decreased BDNF in the hippocampus. In contrast, recombinant human lactoferrin promotes neuronal proliferation by upregulating ERK 1 and 2 phosphorylation and attenuates LPS-induced neuronal injury and microglial activation by inhibiting the activation of Toll-like receptor 4—nuclear factor-kappa B pathway in vitro. Our findings suggest that lactoferrin intake during lactation protects neurons by regulating microglial activation, thereby effectively reducing depressive symptoms in adults.https://doi.org/10.1186/s10020-025-01094-9LactationLactoferrinInflammationDepressionInnate immunityMicroglia |
| spellingShingle | Wenli Wang Qin An Yunxia Zou Yunping Dai Qingyong Meng Yali Zhang Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia Molecular Medicine Lactation Lactoferrin Inflammation Depression Innate immunity Microglia |
| title | Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia |
| title_full | Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia |
| title_fullStr | Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia |
| title_full_unstemmed | Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia |
| title_short | Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia |
| title_sort | lactoferrin alleviates the adverse effects of early life inflammation on depression in adults by regulating the activation of microglia |
| topic | Lactation Lactoferrin Inflammation Depression Innate immunity Microglia |
| url | https://doi.org/10.1186/s10020-025-01094-9 |
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