CSF-1 controls cerebellar microglia and is required for motor function and social interaction.,Journal of Experimental Medicine

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CSF-1 controls cerebellar microglia and is required for motor function and social interaction.
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-07-26 , DOI: 10.1084/jem.20182037
Veronika Kana _{1,

2,

3} , Fiona A Desland _{1,

2,

3} , Maria Casanova-Acebes _{1,

2,

3} , Pinar Ayata _{4,

5} , Ana Badimon _{4,

5} , Elisa Nabel _{4,

6,

7,

8} , Kazuhiko Yamamuro _{4,

6,

7,

8} , Marjolein Sneeboer _{9,

10} , I-Li Tan ₁₁ , Meghan E Flanigan ₄ , Samuel A Rose ₁₂ , Christie Chang _{1,

2,

3} , Andrew Leader _{1,

2,

3} , Hortense Le Bourhis _{1,

2,

3} , Eric S Sweet ₄ , Navpreet Tung _{1,

2,

3} , Aleksandra Wroblewska ₁₂ , Yonit Lavin _{1,

2,

3} , Peter See ₁₃ , Alessia Baccarini ₁₂ , Florent Ginhoux ₁₃ , Violeta Chitu ₁₄ , E Richard Stanley ₁₄ , Scott J Russo ₄ , Zhenyu Yue ₄ , Brian D Brown ₁₂ , Alexandra L Joyner ₁₁ , Lotje D De Witte _{6,

9,

10} , Hirofumi Morishita _{4,

6,

7,

8} , Anne Schaefer _{4,

5} , Miriam Merad _{2,

3,

15}

Affiliation

Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY.
Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY.
Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY.
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY

Microglia, the brain resident macrophages, critically shape forebrain neuronal circuits. However, their precise function in the cerebellum is unknown. Here we show that human and mouse cerebellar microglia express a unique molecular program distinct from forebrain microglia. Cerebellar microglial identity was driven by the CSF-1R ligand CSF-1, independently of the alternate CSF-1R ligand, IL-34. Accordingly, CSF-1 depletion from Nestin+ cells led to severe depletion and transcriptional alterations of cerebellar microglia, while microglia in the forebrain remained intact. Strikingly, CSF-1 deficiency and alteration of cerebellar microglia were associated with reduced Purkinje cells, altered neuronal function, and defects in motor learning and social novelty interactions. These findings reveal a novel CSF-1-CSF-1R signaling-mediated mechanism that contributes to motor function and social behavior.

中文翻译：

CSF-1 控制小脑小胶质细胞，是运动功能和社交互动所必需的。

小胶质细胞是大脑常驻巨噬细胞，对前脑神经元回路具有重要影响。然而，它们在小脑中的确切功能尚不清楚。在这里，我们表明人类和小鼠的小脑小胶质细胞表达了一种不同于前脑小胶质细胞的独特分子程序。小脑小胶质细胞特性由 CSF-1R 配体 CSF-1 驱动，独立于备用 CSF-1R 配体 IL-34。因此，巢蛋白 + 细胞的 CSF-1 耗竭导致小脑小胶质细胞严重耗竭和转录改变，而前脑中的小胶质细胞保持完整。引人注目的是，CSF-1 缺乏和小脑小胶质细胞的改变与浦肯野细胞减少、神经元功能改变以及运动学习和社会新奇互动的缺陷有关。

更新日期：2019-10-07

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