Fourneau Julie, Bareyre Florence M
Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Munich, Germany.
Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München; Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
Neural Regen Res. 2022 May;17(5):959-962. doi: 10.4103/1673-5374.324828.
Serotonin is a monoamine neurotransmitter synthetized in various populations of brainstem neurons. In the spinal cord, descending serotonergic projections regulate postural muscle tone, locomotion and rhythm and coordination of movements via the Central Pattern Generator. Following a spinal cord injury, serotonergic projections to the lumbar spinal cord, where the Central Pattern Generators are located, are interrupted resulting in devastating locomotor impairments and changes in the expression and activation of serotonin and its spinal receptors. The molecular cues that control the precise patterning and targeting of serotonergic inputs onto Central Pattern Generator networks in healthy animals or after injury are still unknown. In our recent research work, we have been particularly interested in Semaphorin7A, which belongs to the Semaphorins family involved in guiding growing axons and controlling plasticity of synaptic connections. In this review, we discuss the role of Semaphorin7A signaling as an important molecular actor that instructs the patterning of serotonin inputs to spinal Central Pattern Generator networks. We show that Semaphorin7A controls the wiring of descending serotonin axons in the spinal cord. Our results reveal that mistargetting of serotonin fibers in the spinal cord is compensated in healthy uninjured Semaphorin7A deficient mice so that their gross locomotion proceeds accurately. We also demonstrate that when the system is challenged with a spinal lesion, the pattern of post-injury serotonin expression is significantly altered in Semaphorin7A deficient mice with specific ectopic targeting of serotonin fibers in the lumbar spinal cord. Compensatory mechanisms in place in uninjured Semaphorin7A deficient mice are lost and injured Semaphorin7A deficient mice exhibit a worsening of their post-injury locomotor abilities. Our findings identify Semaphorin7A as a critical determinant of serotonergic circuit formation in healthy or spinal cord injured mice.
血清素是一种在脑干神经元的不同群体中合成的单胺类神经递质。在脊髓中，下行的血清素能投射通过中枢模式发生器调节姿势肌张力、运动以及运动的节奏和协调性。脊髓损伤后，向位于中枢模式发生器所在位置的腰段脊髓的血清素能投射会中断，导致严重的运动障碍以及血清素及其脊髓受体的表达和激活发生变化。在健康动物或受伤后，控制血清素能输入到中枢模式发生器网络的精确模式和靶向的分子线索仍然未知。在我们最近的研究工作中，我们特别关注了信号素7A，它属于参与引导生长轴突和控制突触连接可塑性的信号素家族。在这篇综述中，我们讨论了信号素7A信号传导作为一个重要分子因子在指导血清素输入到脊髓中枢模式发生器网络模式形成中的作用。我们表明，信号素7A控制脊髓中下行血清素轴突的布线。我们的结果显示，在健康未受伤的信号素7A缺陷小鼠中，脊髓中血清素纤维的错误靶向得到了补偿，因此它们的总体运动能够准确进行。我们还证明，当该系统受到脊髓损伤挑战时，信号素7A缺陷小鼠损伤后血清素的表达模式会发生显著改变，血清素纤维在腰段脊髓中有特定的异位靶向。未受伤的信号素7A缺陷小鼠中存在的补偿机制丧失，受伤的信号素7A缺陷小鼠损伤后的运动能力会恶化。我们的研究结果确定信号素7A是健康或脊髓损伤小鼠血清素能回路形成的关键决定因素。
