Cervical Spinal Cord Injury Upregulates Ventral Spinal 5-HT 2A Receptors

Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Journal of Neurotrauma (Impact Factor: 3.71). 02/2005; 22(2):203-13. DOI: 10.1089/neu.2005.22.203
Source: PubMed


Following chronic C2 spinal hemisection (C2HS), crossed spinal pathways to phrenic motoneurons exhibit a slow, spontaneous increase in efficacy by a serotonin (5-HT)-dependent mechanism associated with 5-HT2A receptor activation. Further, the spontaneous appearance of cross-phrenic activity following C2HS is accelerated and enhanced by exposure to chronic intermittent hypoxia (CIH). We hypothesized that chronic C2HS would increase 5-HT and 5-HT2A receptor expression in ventral cervical spinal segments containing phrenic motoneurons. In addition, we hypothesized that CIH exposure would further increase 5-HT and 5-HT2A receptor density in this region. Control, sham-operated, and C2HS Sprague-Dawley rats were studied following normoxia or CIH (11% O2-air; 5-min intervals; nights 7-14 post-surgery). At 2 weeks post-surgery, ventral spinal gray matter extending from C4 and C5 was isolated ipsilateral and contralateral to C2HS. Neither C2HS nor CIH altered 5-HT concentration measured with an ELISA on either side of the spinal cord. However, 5-HT2A receptor expression assessed with immunoblots increased in ipsilateral gray matter following C2HS, an effect independent of CIH. Immunocytochemistry revealed increased 5-HT2A receptor expression on identified phrenic motoneurons (p<0.05), as well as in the surrounding gray matter. Contralateral to injury, 5-HT2A receptor expression was elevated in CIH, but not normoxic C2HS rats (p<0.05). Our data are consistent with the hypothesis that spontaneous increase in 5-HT2A receptor expression on or near phrenic motoneurons contributes to strengthened crossed-spinal synaptic pathways to phrenic motoneurons following C2HS.

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    • "The loss of 5-HT can be overcome through the direct activation of 5-HT receptors, an approach which has been convincingly associated with the induction of locomotor output following SCI (Brustein and Rossignol, 1999; Feraboli-Lohnherr et al., 1999; Kim et al., 2001b). With the reduction or loss of 5-HT input caudal to the injury in rodent models of SCI, it has been demonstrated that there is a compensatory over-expression of 5-HT receptors (Fuller et al., 2005; Navarrett et al., 2012; Ren et al., 2013). In the lamprey, a vertebrate that exhibits locomotor recovery after complete SCI, a transient over-expression of the 5-HT 1A receptor transcript is observed for several weeks after SCI (Cornide-Petronio et al., 2014). "
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