Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain
Abstract Background Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervou...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-10-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-019-1569-2 |
| _version_ | 1818301913552125952 |
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| author | Matthew Bruce Karin M. Streifel Casey A. Boosalis Luke Heuer Eduardo A. González Shuyang Li Danielle J. Harvey Pamela J. Lein Judy Van de Water |
| author_facet | Matthew Bruce Karin M. Streifel Casey A. Boosalis Luke Heuer Eduardo A. González Shuyang Li Danielle J. Harvey Pamela J. Lein Judy Van de Water |
| author_sort | Matthew Bruce |
| collection | DOAJ |
| description | Abstract Background Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. Methods On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. Results Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. Conclusions These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells. |
| first_indexed | 2024-12-13T05:30:34Z |
| format | Article |
| id | doaj.art-be266a720c564dfe9f3ce55a8b8bfdd2 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-13T05:30:34Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-be266a720c564dfe9f3ce55a8b8bfdd22022-12-21T23:58:05ZengBMCJournal of Neuroinflammation1742-20942019-10-0116111510.1186/s12974-019-1569-2Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brainMatthew Bruce0Karin M. Streifel1Casey A. Boosalis2Luke Heuer3Eduardo A. González4Shuyang Li5Danielle J. Harvey6Pamela J. Lein7Judy Van de Water8MIND Institute, University of California, Davis School of MedicineMIND Institute, University of California, Davis School of MedicineDepartment of Molecular Bioscience, University of California, Davis School of Veterinary MedicineMIND Institute, University of California, Davis School of MedicineDepartment of Molecular Bioscience, University of California, Davis School of Veterinary MedicineDepartment of Public Health Sciences, University of California, Davis School of MedicineDepartment of Public Health Sciences, University of California, Davis School of MedicineMIND Institute, University of California, Davis School of MedicineMIND Institute, University of California, Davis School of MedicineAbstract Background Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. Methods On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. Results Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. Conclusions These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells.http://link.springer.com/article/10.1186/s12974-019-1569-2Rat modelCytokinesMicrogliaAstrocytesSex differencesPeripheral immune challenge |
| spellingShingle | Matthew Bruce Karin M. Streifel Casey A. Boosalis Luke Heuer Eduardo A. González Shuyang Li Danielle J. Harvey Pamela J. Lein Judy Van de Water Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain Journal of Neuroinflammation Rat model Cytokines Microglia Astrocytes Sex differences Peripheral immune challenge |
| title | Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain |
| title_full | Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain |
| title_fullStr | Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain |
| title_full_unstemmed | Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain |
| title_short | Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain |
| title_sort | acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain |
| topic | Rat model Cytokines Microglia Astrocytes Sex differences Peripheral immune challenge |
| url | http://link.springer.com/article/10.1186/s12974-019-1569-2 |
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