title: Orexin A and orexin receptor 1 axonal traffic in dorsal roots at the CNS/PNS interface.
abstract: Hypothalamic orexin/hypocretin neurons send long axonal projections through the dorsal spinal cord in lamina I-II of the dorsal horn (DH) at the interface with the peripheral nervous system (PNS). We show that in the DH OXA fibers colocalize with substance P (SP) positive afferents of dorsal root ganglia (DRG) neurons known to mediate sensory processing. Further, OR1 is expressed in p75(NTR) and SP positive DRG neurons, suggesting a potential signaling pathway between orexin and DRG neurons. Interestingly, DRG sensory neurons have a distinctive bifurcating axon where one branch innervates the periphery and the other one the spinal cord (pseudo-unipolar neurons), allowing for potential functional coupling of distinct targets. We observe that OR1 is transported selectively from DRG toward the spinal cord, while OXA is accumulated retrogradely toward the DRG. We hence report a rare situation of asymmetrical neuropeptide receptor distribution between axons projected by a single neuron. These molecular and cellular data are consistent with the role of OXA/OR1 in sensory processing, including DRG neuronal modulation, and support the potential existence of an OX/HCRT circuit between CNS and PNS.
authors.affiliation: Department of Biology, Stanford University Stanford, CA, USA ; Laboratory of Neurodegeneration and Axon Dynamics, European Brain Research Institute Rome, Italy.
authors.forename: Damien
authors.initials: D
authors.lastname: Colas
authors.affiliation: Laboratory of Neurodegeneration and Axon Dynamics, European Brain Research Institute Rome, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Manca
authors.affiliation: Laboratory of Neurodegeneration and Axon Dynamics, European Brain Research Institute Rome, Italy.
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Delcroix
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Center for Sleep Sciences, Beckman Center, Stanford University Stanford, CA, USA ; INSERM 1024, Ecole Normale Supérieure Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Mourrain
keywords: axonal transport; dorsal root ganglia; hypocretin; nociception; orexin; receptor 1; substance P