Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors
Katherine C Murray, Aya Nakae, Marilee J Stephens, Michelle Rank, Jessica D'Amico, Philip J Harvey, Xiaole Li, R Luke W Harris, Edward W Ballou, Roberta Anelli, Charles J Heckman, Takashi Mashimo, Romana Vavrek, Leo Sanelli, Monica A Gorassini, David J Bennett, Karim Fouad
NATURE MEDICINE | NATURE PUBLISHING GROUP | Published : 2010
Muscle paralysis after spinal cord injury is partly caused by a loss of brainstem-derived serotonin (5-HT), which normally maintains motoneuron excitability by regulating crucial persistent calcium currents. Here we examine how over time motoneurons compensate for lost 5-HT to regain excitability. We find that, months after a spinal transection in rats, changes in post-transcriptional editing of 5-HT2C receptor mRNA lead to increased expression of 5-HT2C receptor isoforms that are spontaneously active (constitutively active) without 5-HT. Such constitutive receptor activity restores large persistent calcium currents in motoneurons in the absence of 5-HT. We show that this helps motoneurons r..View full abstract
Awarded by US National Institutes of Health
Thanks to F. Geddes, T. Tanaka, K. Miyake, G. Van Patten, J. Nevett-Duchcherer, G. Funk, M. Finlay and L. Hahn for assistance. This research was supported by the Alberta Heritage Foundation, Canadian Institutes of Health Research and the US National Institutes of Health (NS47567 and NS48170).