講演タイトル：
Microglia across the lifespan: from neurodevelopment to neurodegeneration

要旨：
Microglia, the resident macrophages of the CNS, play essential roles in both physiological and pathological contexts. They are critical for brain development and the maintenance of homeostasis throughout the lifespan, and are strongly implicated in a wide range of neurological diseases. An increasing body of evidence indicates that many genetic variants associated with elevated risk for neurodegenerative disorders are highly enriched in microglia within the CNS, suggesting that microglial dysfunction may contribute to susceptibility to neurodegeneration. However, the specific mechanisms and developmental timing through which these risk genes influence microglial function and thus promote brain pathology remain poorly understood. Here, we will discuss the diverse roles of microglia during development, highlighting examples of how impaired microglial function can affect brain maturation and lead to long-lasting consequences for neuronal function and behavior. We will also emphasize the relevance of critical developmental windows, proposing a potential link between microglial dysfunction during early postnatal stages and increased vulnerability to neurodegeneration later in life.
 

参考文献：

1. Compagnion AC, I. A., Rana A, Espinoza F, Sandmann T, Martineau FS, Monsorno K, Facchinetti R, Matera A, Rougé L, González Ibáñez F, Catale C, Bizzotto M, Garel S, Matteoli M, Kashiwagi Y, Koyama R, Haass C, Tremblay ME, Beule D, Jelescu I, Zerbi V, Di Paolo G and Paolicelli RC. Microglial TDP-43 mediates myelin refinement and represses Tyrobp cryptic exon inclusion in mice. Nat Neurosci, in press, 2026.
2. Petrelli F, Gilardi C, Igelbüscher CM, Panfilova D, Rey A, Paolicelli RC, Knobloch M. Cellular mechanisms of brain lipid metabolism in health and disease. Nat Cell Biol. 2026 Feb 20. Epub ahead of print.
3. Matera A, Compagnion AC, Pedicone C, Kotah JM, Ivanov A, Monsorno K, Labouèbe G, Leggio L, Pereira-Iglesias M, Beule D, Mansuy-Aubert V, Williams TL, Iraci N, Sierra A, Marro SG, Goate AM, Eggen BJL, Kerr WG, Paolicelli RC. Microglial lipid phosphatase SHIP1 limits complement-mediated synaptic pruning in the healthy developing hippocampus. Immunity. 2025 Jan 14;58(1):197-217.e13.
4. Lv Z, Chen L, Chen P, Peng H, Rong Y, Hong W, Zhou Q, Li N, Li B, Paolicelli RC, Zhan Y. Clearance of β-amyloid and synapses by the optogenetic depolarization of microglia is complement selective. Neuron. 2024 Mar 6;112(5):740-754.e7.
5. Monsorno K, Ginggen K, Ivanov A, Buckinx A, Lalive AL, Tchenio A, Benson S, Vendrell M, D'Alessandro A, Beule D, Pellerin L, Mameli M, Paolicelli RC. Loss of microglial MCT4 leads to defective synaptic pruning and anxiety-like behavior in mice. Nat Commun. 2023 Sep 16;14(1):5749.
6. Paolicelli RC, Sierra A, Stevens B, Tremblay ME et al. Microglia states and nomenclature: A field at its crossroads. Neuron. 2022 Nov 2;110(21):3458-3483.

世話人：
生体防御医学研究所　分子神経免疫学分野 増田隆博

092-642-6800 takahiro.masuda@bioreg.kyushu-u.ac.jp

Division of Molecular Neuroimmunology, Medical Institute of Bioregulation

Takahiro Masuda

講演タイトル：
Tracking reactive microglial state across the lifespan

要旨：
Single-cell RNA sequencing studies have revealed transcriptionally distinct microglial states across development, aging, and disease. These include proliferative region–associated microglia (PAMs) in the developing white matter, disease-associated microglia (DAMs) common to many neurodegenerative conditions, and white matter–associated microglia (WAMs) in the aged brain, among others. Interestingly, PAMs, DAMs, and WAMs share a core gene signature and overlapping functional properties. However, it remains unclear whether these subsets represent ontogenically distinct lineages or instead reflect plastic transitions of microglial states driven by converging signals. The temporal dynamics, regulatory mechanisms, and functional implications of microglial state changes also remain poorly understood. Using a specific inducible driver line, Clec7a-CreERT2, recently developed by us, we track PAMs and DAMs across conditions and lifespan, revealing the extraordinary plasticity of reactive microglial states. We further employ highly sensitive epigenomic profiling to identify the cis- and trans-regulatory elements that govern these transitions. These studies uncover the intricate relationships and dynamic nature of spatially and temporally discrete microglial states in health and disease.

参考文献：
1. Li Q*, Cheng Z, Zhou L, Darmanis S, Neff NF, Okamoto J, Gulati G, Bennett ML, Sun LO, Clarke LE, Marschallinger J, Yu G, Quake SR, Wyss-Coray T, Barres BA. Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing. Neuron. 2019 Jan 16;101(2):207-223.e10. PMCID: PMC6336504.
2. Barclay KM, Abduljawad N, Cheng Z, Kim MW, Zhou L, Yang J, Rustenhoven J, Mazzitelli Perez J, Smyth LCD, Kapadia D, Brioschi S, Beatty W, Hou JC, Saligrama N, Colonna M, Yu G, Kipnis J, Li Q*. An inducible genetic tool for tracking and manipulating specific microglial states in development and disease. Immunity. 2024 Jun 11;57(6):1394-1412.e8. PubMed PMID: 38821054; NIHMSID:NIHMS1999302.
3. Hamagami N, Kapadia D, Barclay KM, Huang Y, Abduljawad N, Cheng Z, McLaughlin L, Singhania D, Ding X, Yang J, Sun Z, Karra V, Du S, Bayguinov P, Yu G, Li YE, Gabel HW*, Li Q*. State-specific enhancer landscapes govern microglial plasticity. Immunity. 2026 Jan 7; doi: 10.1016/j.immuni.2025.11.023
4. Naz H, Palovics R, Yamada S, Lu N, Wyss-Coray T, Li Q*, Zhao G*. Core activation program and selective responsiveness of microglia in aging and parabiosis. bioRxiv. 2025. In revision.
doi:https://doi.org/10.1101/2025.10.29.685417


世話人：生体防御医学研究所　分子神経免疫学分野 増田隆博

092-642-6800 takahiro.masuda@bioreg.kyushu-u.ac.jp

Division of Molecular Neuroimmunology, Medical Institute of Bioregulation

Takahiro Masuda

・日時：令和8年8月22日（土）14：00～16：00
・開催方式：ZOOM（オンライン開催）
・申し込み方法：事前申し込み制（下記参加申し込みフォームより必要事項を入力の上、送信してください）
　　　 　　　（8月17日締め切り）
 
〇講演Ⅰ： 演者　秦　淳先生（九州大学大学院医学研究院医療経営・管理学 教授）

〇講演Ⅱ： 演者　堀 　裕行先生（厚生労働省 老健局老人保健課長）

※演題名等は追って掲載します

〇お問合せ先
九州大学大学院医学研究院 医療経営・管理学講座（立石）
〒812-8582　福岡市東区馬出3丁目1-1
Tel：092-642-6960　Fax：092-642-6961
E-MAIL：tateishi.yuko.161@m.kyushu-u.ac.jp
URL：https://www.hcam.med.kyushu-u.ac.jp/

【イベント詳細】
主　　催　九州大学医学部保健学科
講　　演　①臨床検査から始まる医療
　　　　　　（八木　美佳子　検査技術科学専攻助教）
　　　　　②最新CT技術と診療放射線技師が変える医療現場
　　　　　　（小島　宰　放射線技術科学専攻講師）
　　　　　③医療DX時代の看護職の役割
　　　　　　（潮　みゆき　看護学専攻講師）
対　　象　高校生、地域の方
参加方法　会場参加（先着100名）
　　　　　オンライン参加（先着300名）
開催日時　2026年9月13日（日）13:30～15:30 ※開場13:00　


【問い合わせ先】　
担当：九州大学医系学部等事務部総務課総務第一係
電話：092-642-6249
Mail：ijssomu1★jimu.kyushu-u.ac.jp
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