小柯机器人

意大利IRCCS Humanitas研究医院Michela Matteoli小组发现，小胶质细胞中Trem2的表达是发育过程中维持正常神经元生物能所需。相关论文于2023年12月29日在线发表于国际学术期刊《免疫》。

研究人员证明髓系细胞上表达的触发受体2（Trem2）在控制锥体神经元发育过程中的生物能谱方面起着关键作用。在Trem2缺失的情况下，海马cornus ammonis（CA）1而非CA3分区的发育中神经元表现出能量代谢受损，同时线粒体质量降低和细胞器超微结构异常。

与此同时，出生时海马锥体神经元的转录也发生了重新排列，代谢、氧化磷酸化和线粒体基因特征发生了普遍改变，同时CA1神经元的成熟也出现了延迟。这些研究结果揭示了Trem2在控制神经元发育中的作用，它以区域特异性的方式调节神经元的代谢适应性。

据悉，Trem2是一种在脑小胶质细胞中表达的髓系细胞特异基因，其变体与神经退行性疾病（包括阿尔茨海默病）有关。Trem2对小胶质细胞介导的突触细化至关重要，但Trem2是否有助于塑造神经元发育仍不清楚。

附：英文原文

Title: Trem2 expression in microglia is required to maintain normal neuronal bioenergetics during development

Author: Erica Tagliatti, Genni Desiato, Sara Mancinelli, Matteo Bizzotto, Maria C. Gagliani, Elisa Faggiani, Rebeca Hernández-Soto, Andrea Cugurra, Paola Poliseno, Matteo Miotto, Rafael J. Argüello, Fabia Filipello, Katia Cortese, Raffaella Morini, Simona Lodato, Michela Matteoli

Issue&Volume: 2023-12-29

Abstract: Triggering receptor expressed on myeloid cells 2 (Trem2) is a myeloid cell-specific gene expressed in brain microglia, with variants that are associated with neurodegenerative diseases, including Alzheimer’s disease. Trem2 is essential for microglia-mediated synaptic refinement, but whether Trem2 contributes to shaping neuronal development remains unclear. Here, we demonstrate that Trem2 plays a key role in controlling the bioenergetic profile of pyramidal neurons during development. In the absence of Trem2, developing neurons in the hippocampal cornus ammonis (CA)1 but not in CA3 subfield displayed compromised energetic metabolism, accompanied by reduced mitochondrial mass and abnormal organelle ultrastructure. This was paralleled by the transcriptional rearrangement of hippocampal pyramidal neurons at birth, with a pervasive alteration of metabolic, oxidative phosphorylation, and mitochondrial gene signatures, accompanied by a delay in the maturation of CA1 neurons. Our results unveil a role of Trem2 in controlling neuronal development by regulating the metabolic fitness of neurons in a region-specific manner.

DOI: 10.1016/j.immuni.2023.12.002

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00533-2

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