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