IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
Cell Death Dis. 2011 Oct 13;2(10):e218. doi: 10.1038/cddis.2011.98.
Serotonergic innervation of the spinal cord in mammals has multiple roles in the control of motor, sensory and visceral functions. In rats, functional consequences of spinal cord injury at thoracic level can be improved by a substitutive transplantation of serotonin (5-HT) neurons or regeneration under the trophic influence of grafted stem cells. Translation to either pharmacological and/or cellular therapies in humans requires the mapping of the spinal cord 5-HT innervation and its receptors to determine their involvement in specific functions. Here, we have performed a preliminary mapping of serotonergic processes and serotonin-lA (5-HT(1A)) receptors in thoracic and lumbar segments of the human spinal cord. As in rodents and non-human primates, 5-HT profiles in human spinal cord are present in the ventral horn, surrounding motoneurons, and also contact their presumptive dendrites at lumbar level. 5-HT(1A) receptors are present in the same area, but are more densely expressed at lumbar level. 5-HT profiles are also present in the intermediolateral region, where 5-HT(1A) receptors are absent. Finally, we observed numerous serotonergic profiles in the superficial part (equivalent of Rexed lamina II) of the dorsal horn, which also displayed high levels of 5-HT(1A) receptors. These findings pave the way for local specific therapies involving cellular and/or pharmacological tools targeting the serotonergic system.
哺乳动物脊髓中的 5-羟色胺能神经支配在运动、感觉和内脏功能的控制中具有多种作用。在大鼠中,通过替代移植 5-羟色胺(5-HT)神经元或在移植干细胞的营养影响下再生,可以改善胸段脊髓损伤的功能后果。要在人类中进行药物和/或细胞治疗的转化,需要对脊髓 5-HT 支配及其受体进行映射,以确定它们在特定功能中的参与。在这里,我们对人类脊髓的胸段和腰段进行了 5-羟色胺能过程和 5-羟色胺-1A(5-HT1A)受体的初步映射。与啮齿动物和非人类灵长类动物一样,人类脊髓中的 5-HT 图谱存在于腹角中,环绕运动神经元,并且在腰段也与它们假定的树突接触。5-HT1A 受体存在于相同区域,但在腰段表达更为密集。5-HT 图谱也存在于中间外侧区域,其中不存在 5-HT1A 受体。最后,我们在背角的浅层(相当于雷克斯德层 II)观察到许多 5-羟色胺能图谱,这些图谱也显示出 5-HT1A 受体的高水平。这些发现为涉及针对 5-羟色胺能系统的细胞和/或药物工具的局部特定治疗铺平了道路。