Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil; Núcleo Multidisciplinar de Pesquisa em Biologia (Numpex-Bio), Campus de Duque de Caxias Geraldo Guerra Cidade, Universidade Federal do Rio de Janeiro, Duque de Caxias, RJ 25255-030, Brazil.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
Brain Behav Immun. 2022 Feb;100:183-193. doi: 10.1016/j.bbi.2021.12.004. Epub 2021 Dec 8.
Neural-immune interactions are related to the synapse plasticity and other dynamic processes in the nervous system. The absence or dysfunction of cellular/molecular elements from the immune system lead to impairments in the central and peripheral nervous system with behavior consequences such as cognitive, sensory, and locomotor deficits as well as social disabilities and anxiety disturbances. Cellular interactions between immune cells such as macrophages, microglia, and neutrophils with glial or neuronal cells have been of increasing interest over the last years. However, little is known about the role of immune-derived soluble factors in the context of homeostasis of the nervous system. Leukotrienes (LTs) are lipid mediators derived from the oxidation of arachidonic acid by 5-lipoxygenase (5-LO), and are classically involved in inflammation, allergies, and asthma. Here, we demonstrated that adult mice lacking 5-LO (5-LO) showed motor deficits in rotarod test and increased repetitive behavior (marble burying test). These behavioral changes are accompanied by increased levels of synapse proteins (PSD95 and synaptophysin) at the motor cortex and hippocampus, but not with BDNF alterations. No changes in microglial cell density or morphology were seen in the brains of 5-LO mice. Furthermore, expression of fractalkine receptor CX3CR1 was increased and of its ligand CX3CL1 was decreased in the cortex of 5-LO mice. Here we provide evidence for the involvement of 5-LO products structuring synapses network with motor behavior consequences. We suggest that the absence of 5-LO products lead to modified microglial/neuron interaction, reducing microglial pruning.
神经免疫相互作用与突触可塑性和神经系统中的其他动态过程有关。免疫系统中细胞/分子元素的缺失或功能障碍会导致中枢和外周神经系统受损，从而导致认知、感觉和运动功能障碍以及社交障碍和焦虑障碍等行为后果。近年来，免疫细胞（如巨噬细胞、小胶质细胞和中性粒细胞）与神经胶质细胞或神经元细胞之间的细胞相互作用引起了越来越多的关注。然而，对于免疫源性可溶性因子在神经系统稳态中的作用知之甚少。白三烯（LTs）是花生四烯酸经 5-脂氧合酶（5-LO）氧化衍生的脂质介质，经典地参与炎症、过敏和哮喘。在这里，我们证明缺乏 5-LO（5-LO）的成年小鼠在转棒试验中表现出运动功能障碍和重复性行为增加（埋珠试验）。这些行为变化伴随着运动皮层和海马体中突触蛋白（PSD95 和突触小体）水平的升高，但 BDNF 没有改变。5-LO 小鼠大脑中的小胶质细胞密度或形态没有变化。此外，5-LO 小鼠大脑皮质中 fractalkine 受体 CX3CR1 的表达增加，其配体 CX3CL1 减少。在这里，我们提供了证据证明 5-LO 产物参与构建与运动行为后果相关的突触网络。我们认为 5-LO 产物的缺失会导致小胶质细胞/神经元相互作用改变，减少小胶质细胞修剪。
