title: HuD-mediated distinct BDNF regulatory pathways promote regeneration after nerve injury.
abstract: Up-regulation of brain-derived neurotrophic factor (BDNF) synthesis is an important mechanism of peripheral nerve regeneration after injury. However, the cellular and molecular mechanisms underlying this process are not fully understood. This study examines the role of BDNF in the spared nerve injury (SNI) mice model. Protein expression and cellular localization were investigated in the dorsal root ganglia (DRG) and spinal cord by western blotting and immunofluorescence experiments respectively. BDNF protein was markedly increased 3 and 7days post-injury in the spinal cord and DRG. Following nerve injury sensory neurons produce molecules to promote regeneration, such as growth-associated protein 43 (GAP-43) and cytoskeletal proteins. Our results show that the expression of GAP-43 was increased in the DRG and spinal cord while, an increased of p-NFH content was detected in the spinal cord, with no modification in the DRG. Both events were counteracted by the administration of an anti-BDNF antibody. In DRG of SNI mice we also detected an increase of HuD expression, a RNA-binding protein known to stabilize BDNF and GAP-43 mRNA. Silencing of HuD prevented the nerve injury-induced BDNF and GAP-43 enhanced expression in the DRG. HuD-mediated BDNF synthesis in the primary sensory neurons, is followed by an anterograde transport of the neurotrophin to the central terminals of the primary afferents in the spinal dorsal horn, to modulate GAP-43 and NFH activation. Our data suggest that BDNF, GAP-43 and p-NFH proteins increase are linked events required for the enhanced regeneration after nerve injury.
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, Viale G. Pieraccini 6, 50139 Florence, Italy. Electronic address: maria.sanna@unifi.it.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Sanna
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, Viale G. Pieraccini 6, 50139 Florence, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, Viale G. Pieraccini 6, 50139 Florence, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Galeotti
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004195:Disease Models, Animal; D000067779:ELAV-Like Protein 4 / Q000378:metabolism*; D019922:GAP-43 Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology*; D016900:Neurofilament Proteins / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000067779:ELAV-Like Protein 4; C498011:Elavl4 protein, mouse; D019922:GAP-43 Protein; D016900:Neurofilament Proteins; D012333:RNA, Messenger; C051774:neurofilament protein H
keywords: BDNF; GAP-43; HuD; Nerve-injury-induced regeneration; Neurofilament