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Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons

Geremia, Nicole M.; Pettersson, Lina LU ; Hasmatali, J. C.; Hryciw, Todd; Danielsen, Nils LU ; Schreyer, David J. and Verge, Valerie M. K. (2010) In Experimental Neurology 223(1). p.128-142
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... (More)
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 T alpha 1 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. (C) 2009 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Regeneration, GAP-43, Sensory neuron, Neurotrophin, Peripheral nerve
in
Experimental Neurology
volume
223
issue
1
pages
128 - 142
publisher
Academic Press
external identifiers
  • wos:000277377000016
  • scopus:77950857666
ISSN
0014-4886
DOI
10.1016/j.expneurol.2009.07.022
language
English
LU publication?
yes
id
fa214474-1869-4bc4-aca3-dc795016a21d (old id 1618611)
date added to LUP
2010-06-18 16:17:19
date last changed
2018-06-17 03:27:28
@article{fa214474-1869-4bc4-aca3-dc795016a21d,
  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 T alpha 1 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. (C) 2009 Elsevier Inc. All rights reserved.},
  author       = {Geremia, Nicole M. and Pettersson, Lina and Hasmatali, J. C. and Hryciw, Todd and Danielsen, Nils and Schreyer, David J. and Verge, Valerie M. K.},
  issn         = {0014-4886},
  keyword      = {Regeneration,GAP-43,Sensory neuron,Neurotrophin,Peripheral nerve},
  language     = {eng},
  number       = {1},
  pages        = {128--142},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2009.07.022},
  volume       = {223},
  year         = {2010},
}