title: The time course of serotonin 2A receptor expression after spinal transection of rats: an immunohistochemical study.
abstract: Hyperexcitability of motoneurons is one of the key mechanism that has been demonstrated to underlie the pathogenesis of spasticity after spinal injury. Serotonin (5-HT) denervation supersensitivity is one of the mechanisms underlying this increased motoneuron excitability. In this study, to examine whether the supersensitivity is caused by 5-HT receptor upregulation we investigated changes in levels of 5-HT2A receptor immunoreactivity (5-HT2AR-IR) following a spinal transection in the sacral spinal cord of rats at seven different time points post injury: 2, 8, 16 h, and 1, 2, 7 and 28 days, respectively. 5-HT2AR-IR density was analyzed in motoneurons (regions containing their somata and dendrites) in the spinal segments below the lesion. The results showed no significant changes in 5-HT2AR-IR in the motoneurons up to 16 h following the transection. After 1-day, however the levels of 5-HT2AR-IR increased in the motoneurons and their dendrites, with the density level being 3.4-fold higher in spinalized rats than in sham-operated rats. The upregulation increased progressively until a maximal level was reached at 28 days post-injury. We also investigated 5-HT and 5-HT transporter expressions at five different post injury time points: 1, 2, 7, 21 and 60 days and they showed concurrent down-regulation changes after 2 days. These results suggest that the upregulation of 5-HT2ARs may at least partly underlie the development of 5-HT denervation supersensitivity in spinal motoneurons following spinal injury and thereby implicates their involvement in the pathogenesis of the subsequent development of spasticity.
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen, Denmark.
authors.forename: X-Y
authors.initials: XY
authors.lastname: Kong
authors.forename: J
authors.initials: J
authors.lastname: Wienecke
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Hultborn
authors.forename: M
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004525:Efferent Pathways / Q000737:chemistry / Q000293:injuries / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009046:Motor Neurons / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D009128:Muscle Spasticity / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010264:Paraplegia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000096:biosynthesis*; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D044402:Receptor, Serotonin, 5-HT2A