TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus
Open accessAbstract
Pathological conditions such as epilepsy cause misregulation of adult neural stem/progenitor populations in the adult hippocampus in mice, and the resulting abnormal neurogenesis leads to impairment in learning and memory. However, how animals cope with abnormal neurogenesis remains unknown. Here we show that microglia in the mouse hippocampus attenuate convulsive seizure-mediated aberrant neurogenesis through the activation of Toll-like receptor 9 (TLR9), an innate immune sensor known to recognize microbial DNA and trigger inflammatory responses. We found that microglia sense self-DNA from degenerating neurons following seizure, and secrete tumour necrosis factor-α, resulting in attenuation of aberrant neurogenesis. Furthermore, TLR9 deficiency exacerbated seizure-induced cognitive decline and recurrent seizure severity. Our findings thus suggest the existence of bidirectional communication between the innate immune and nervous systems for the maintenance of adult brain integrity.
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DNA derived from degenerating neurons evokes NF-κB activation in microglia via TLR9.
“DNA derived from degenerating neurons evokes NF-κB activation in microglia via TLR9.318”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [318]
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- Authors
- Matsuda, T., Murao, N., Katano, Y., Juliandi, B., Kohyama, J., Akira, S., Kawai, T., & Nakashima, K.
- Affiliations
- Kyushu University (JP)
- Keio University (JP)
- Immunology Frontier Research Center, The University of Osaka (JP)
- Nara Institute of Science and Technology (JP)
- Corresponding author
- Nakashima, Kinichi
- ORCID
- Venue
- Nature Communications
- Published
- 2015-03-09
- Volume
- 6
- Issue
- 1
- Pages
- 6514-6514
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4366529
- OpenAlex
- W2094923592
- Cited by
- 145
- References
- 48
- Citations by year
- 2026: 15 · 2025: 13 · 2024: 17 · 2023: 13 · 2022: 18 · 2021: 10 · 2020: 9 · 2019: 13 · 2018: 10 · 2017: 10 · 2016: 14 · 2015: 3
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Asahi Glass Foundation
- Ministry of Education, Culture, Sports, Science and Technology (CREST)
- Japan Society for the Promotion of Science (24650198, 13J09007, CREST, 26713047, 15H06474)
- Japan Science and Technology Agency (CREST)
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- TLR9, microglia, adult hippocampus, epilepsy, TNF-α, innate immune response, cognitive decline, recurrent seizures, neuroinflammation, neural stem/progenitor cells
- MeSH terms
- Animals, Cognition, Gene Expression Regulation, Hippocampus, Immunity, Innate, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Neurons, Seizures, Severity of Illness Index, Tumor Necrosis Factor-alpha, Signal Transduction, Microglia, Mice, Knockout, Toll-Like Receptor 7, Toll-Like Receptor 9, Mice, Neurogenesis, Cognitive Dysfunction
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