The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34
Abstract Microglia harness an unutilized health-promoting potential in age-related neurodegenerative and neuroinflammatory diseases, conditions like progressive multiple sclerosis (MS). Our research unveils an microglia population emerging in the cortical brain regions of aging mice, marked by ERK1/...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44556-6 |
| _version_ | 1797355672357044224 |
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| author | Rasmus Berglund Yufei Cheng Eliane Piket Milena Z. Adzemovic Manuel Zeitelhofer Tomas Olsson Andre Ortlieb Guerreiro-Cacais Maja Jagodic |
| author_facet | Rasmus Berglund Yufei Cheng Eliane Piket Milena Z. Adzemovic Manuel Zeitelhofer Tomas Olsson Andre Ortlieb Guerreiro-Cacais Maja Jagodic |
| author_sort | Rasmus Berglund |
| collection | DOAJ |
| description | Abstract Microglia harness an unutilized health-promoting potential in age-related neurodegenerative and neuroinflammatory diseases, conditions like progressive multiple sclerosis (MS). Our research unveils an microglia population emerging in the cortical brain regions of aging mice, marked by ERK1/2, Akt, and AMPK phosphorylation patterns and a transcriptome indicative of activated autophagy - a process critical for cellular adaptability. By deleting the core autophagy gene Ulk1 in microglia, we reduce this population in the central nervous system of aged mice. Notably, this population is found dependent on IL-34, rather than CSF1, although both are ligands for CSF1R. When aging mice are exposed to autoimmune neuroinflammation, the loss of autophagy-dependent microglia leads to neural and glial cell death and increased mortality. Conversely, microglial expansion mediated by IL-34 exhibits a protective effect. These findings shed light on an autophagy-dependent neuroprotective microglia population as a potential target for treating age-related neuroinflammatory conditions, including progressive MS. |
| first_indexed | 2024-03-08T14:14:29Z |
| format | Article |
| id | doaj.art-b61d9e7702d14043bf1b0b3ca392caef |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T14:14:29Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b61d9e7702d14043bf1b0b3ca392caef2024-01-14T12:29:13ZengNature PortfolioNature Communications2041-17232024-01-0115111910.1038/s41467-023-44556-6The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34Rasmus Berglund0Yufei Cheng1Eliane Piket2Milena Z. Adzemovic3Manuel Zeitelhofer4Tomas Olsson5Andre Ortlieb Guerreiro-Cacais6Maja Jagodic7Department of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Center for Molecular Medicine, Karolinska University HospitalDepartment of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Center for Molecular Medicine, Karolinska University HospitalDepartment of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Center for Molecular Medicine, Karolinska University HospitalDepartment of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Center for Molecular Medicine, Karolinska University HospitalDepartment of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska InstitutetDepartment of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Center for Molecular Medicine, Karolinska University HospitalDepartment of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Center for Molecular Medicine, Karolinska University HospitalDepartment of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Center for Molecular Medicine, Karolinska University HospitalAbstract Microglia harness an unutilized health-promoting potential in age-related neurodegenerative and neuroinflammatory diseases, conditions like progressive multiple sclerosis (MS). Our research unveils an microglia population emerging in the cortical brain regions of aging mice, marked by ERK1/2, Akt, and AMPK phosphorylation patterns and a transcriptome indicative of activated autophagy - a process critical for cellular adaptability. By deleting the core autophagy gene Ulk1 in microglia, we reduce this population in the central nervous system of aged mice. Notably, this population is found dependent on IL-34, rather than CSF1, although both are ligands for CSF1R. When aging mice are exposed to autoimmune neuroinflammation, the loss of autophagy-dependent microglia leads to neural and glial cell death and increased mortality. Conversely, microglial expansion mediated by IL-34 exhibits a protective effect. These findings shed light on an autophagy-dependent neuroprotective microglia population as a potential target for treating age-related neuroinflammatory conditions, including progressive MS.https://doi.org/10.1038/s41467-023-44556-6 |
| spellingShingle | Rasmus Berglund Yufei Cheng Eliane Piket Milena Z. Adzemovic Manuel Zeitelhofer Tomas Olsson Andre Ortlieb Guerreiro-Cacais Maja Jagodic The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34 Nature Communications |
| title | The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34 |
| title_full | The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34 |
| title_fullStr | The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34 |
| title_full_unstemmed | The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34 |
| title_short | The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34 |
| title_sort | aging mouse cns is protected by an autophagy dependent microglia population promoted by il 34 |
| url | https://doi.org/10.1038/s41467-023-44556-6 |
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