Department of Biomedical Sciences, Humanitas University, Milan, Italy.
Neuro Center, IRCCS Humanitas Research Hospital, Milan, Italy.
Glia. 2024 Sep;72(9):1544-1554. doi: 10.1002/glia.24574. Epub 2024 Jun 5.
The nervous and the immune systems undergo a continuous cross talk, starting from early development and continuing throughout adulthood and aging. Defects in this cross talk contribute to neurodevelopmental and neurodegenerative diseases. Microglia are the resident immune cells in the brain that are primarily involved in this bidirectional communication. Among the microglial genes, trem2 is a key player, controlling the functional state of microglia and being at the forefront of many processes that require interaction between microglia and other brain components, such as neurons and oligodendrocytes. The present review focuses on the early developmental window, describing the early brain processes in which TREM2 is primarily involved, including the modulation of synapse formation and elimination, the control of neuronal bioenergetic states as well as the contribution to myelination processes and neuronal circuit formation. By causing imbalances during these early maturation phases, dysfunctional TREM2 may have a striking impact on the adult brain, making it a more sensitive target for insults occurring during adulthood and aging.
神经系统和免疫系统经历持续的交叉对话，从早期发育开始，并持续到成年和衰老。这种交叉对话的缺陷导致神经发育和神经退行性疾病。小胶质细胞是大脑中的常驻免疫细胞，主要参与这种双向通讯。在小胶质细胞基因中，TREM2 是一个关键的参与者，控制着小胶质细胞的功能状态，并处于许多需要小胶质细胞与其他大脑成分（如神经元和少突胶质细胞）相互作用的过程的前沿。本综述重点关注早期发育窗口，描述 TREM2 主要参与的早期大脑过程，包括突触形成和消除的调节、神经元生物能量状态的控制以及对髓鞘形成过程和神经元回路形成的贡献。通过在这些早期成熟阶段造成失衡，功能失调的 TREM2 可能对成年大脑产生显著影响，使其成为成年和衰老期间发生的损伤的更敏感的靶标。
