title: Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons.
abstract: Identification of the molecule(s) that globally induce a robust regenerative state in sensory neurons following peripheral nerve injury remains elusive. A potential candidate is brain-derived neurotrophic factor (BDNF), the sole neurotrophin upregulated in sensory neurons after peripheral nerve injury. Here we tested the hypothesis that BDNF plays a critical role in the regenerative response of mature rat sensory neurons following peripheral nerve lesion. Neutralization of endogenous BDNF was performed by infusing BDNF antibodies intrathecally via a mini-osmotic pump for 3 days at the level of the fifth lumbar dorsal root ganglion, immediately following unilateral spinal nerve injury. This resulted in decreased expression of the injury/regeneration-associated genes growth-associated protein-43 and Talpha1 tubulin in the injured sensory neurons as compared to injury plus control IgG infused or injury alone animals. Similar results were observed following inhibition of BDNF expression by intrathecal delivery of small interfering RNAs (siRNA) targeting BDNF starting 3 days prior to injury. The reduced injury/regeneration-associated gene expression correlated with a significantly reduced intrinsic capacity of these neurons to extend neurites when assayed in vitro. In contrast, delayed infusion of BDNF antibody for 3 days beginning 1 week post-lesion had no discernible influence on the elevated expression of these regeneration-associated markers. These results support an important role for endogenous BDNF in induction of the cell body response in injured sensory neurons and their intrinsic ability to extend neurites, but BDNF does not appear to be necessary for maintaining the response once it is induced.
authors: Department of Anatomy and Cell Biology, Cameco MS Neuroscience Research Center University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E5.
authors: Nicole M
authors: NM
authors: Geremia
authors: Lina M E
authors: LM
authors: Pettersson
authors: J C
authors: JC
authors: Hasmatali
authors: Todd
authors: T
authors: Hryciw
authors: Nils
authors: N
authors: Danielsen
authors: David J
authors: DJ
authors: Schreyer
authors: Valerie M K
authors: VM
authors: Verge
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007074:Immunoglobulin G / Q000494:pharmacology; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D016501:Neurites / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D013997:Time Factors; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D007074:Immunoglobulin G; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014404:Tubulin