Abstract

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-HT1A) 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-HT1A 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-HT1A 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-HT1A receptors. These findings pave the way for local specific therapies involving cellular and/or pharmacological tools targeting the serotonergic system.

Highlights

  • Locomotion has been found to result from the activation of a central pattern generator (CPG; for review see Grillner[1])

  • At thoracic level, immunostaining of serotonin or 5-hydroxytryptamine (5-HT) appears clearly limited to three regions of the gray matter, namely the superficial part of the dorsal horn, the intermediolateral (IML) area and the ventral horn around motoneurons (Figure 1a)

  • At lumbar level, immunostaining of 5-HT appears most intense in the ventral horn, with more discrete profiles in the dorsal horn and the IML area (Figure 2a)

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Summary

Introduction

Locomotion has been found to result from the activation of a central pattern generator (CPG; for review see Grillner[1]). The control of the genito-urinary tract has been found to be largely mediated by 5-HT11–13 as well as the central command for ejaculation, which has been located at thoraco–lumbar and lumbo–sacral levels of the spinal cord.[14]. Both locomotor and ejaculatory controls have been found to be mediated through the activation of 5-HT1 receptors.[11,15,16,17] spinal control of nociception involves serotonergic projections to the dorsal horn of rats through 5-HT1 receptors.[18,19,20]. Experimental models may serve as a basis for therapeutic strategies aiming at repairing the injured spinal cord in humans

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