title: Neuronal death in the dorsal root ganglion after sciatic nerve injury does not depend on sortilin.
abstract: Injury to the sciatic nerve induces loss of sensory neurons in the affected dorsal root ganglia (DRGs). Previous studies have suggested the involvement of the neurotrophin receptors p75 neurotrophin receptor (p75(NTR)) and sortilin, proposing that sensory neuron subpopulations undergo proneurotrophin-induced apoptosis in a similar manner to what can be observed in the CNS following injury. To further investigate this hypothesis we induced sciatic nerve injury in sortilin-deficient mice, thereby preventing apoptotic signaling of proneurotrophins via the sortilin-p75(NTR) receptor complex. Using an unbiased stereological approach we found that loss of sortilin did not prevent the injury-induced loss of DRG neurons. This result demonstrates that previous findings linking p75(NTR) and proneurotrophins to loss of sensory neurons need to involve sortilin-independent pathways and suggests that proneurotrophins may elicit different functions in the CNS and PNS.
authors.affiliation: The Lundbeck Foundation Research Center Mind, Department of Biomedicine, Aarhus University, Ole Worms Allé 3, Aarhus DK-8000, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Gürgör
authors.affiliation: The Lundbeck Foundation Research Center Mind, Department of Biomedicine, Aarhus University, Ole Worms Allé 3, Aarhus DK-8000, Denmark.
authors.forename: L T
authors.initials: LT
authors.lastname: Pallesen
authors.affiliation: The Lundbeck Foundation Research Center Mind, Department of Biomedicine, Aarhus University, Ole Worms Allé 3, Aarhus DK-8000, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Johnsen
authors.affiliation: The Lundbeck Foundation Research Center Mind, Department of Biomedicine, Aarhus University, Ole Worms Allé 3, Aarhus DK-8000, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Ulrichsen
authors.affiliation: H. Lundbeck A/S, Division of Neurodegeneration, Ottiliavej 9, Valby DK-2500, Denmark.
authors.forename: I E M
authors.initials: IE
authors.lastname: de Jong
authors.affiliation: The Lundbeck Foundation Research Center Mind, Department of Biomedicine, Aarhus University, Ole Worms Allé 3, Aarhus DK-8000, Denmark. Electronic address: cv@biomed.au.dk.
authors.forename: C B
authors.initials: CB
authors.lastname: Vaegter
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000473:pathology*; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D020800:Receptor, Nerve Growth Factor; D000099183:Sortilin
keywords: cell death; dorsal root ganglion; injury; p75(NTR); sortilin