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Injury-associated PACAP expression in rat sensory and motor neurons is induced by endogenous BDNF

Pettersson, Lina M E LU ; Geremia, Nicole M; Ying, Zhengxin and Verge, Valerie M K (2014) In PLoS One 9(6). p.100730-100730
Abstract

Peripheral nerve injury results in dramatic upregulation in pituitary adenylate cyclase activating polypeptide (PACAP) expression in adult rat dorsal root ganglia and spinal motor neurons mirroring that described for the neurotrophin brain derived neurotrophic factor (BDNF). Thus, we posited that injury-associated alterations in BDNF expression regulate the changes in PACAP expression observed in the injured neurons. The role of endogenous BDNF in induction and/or maintenance of PACAP mRNA expression in injured adult rat motor and sensory neurons was examined by intrathecally infusing or intraperitoneally injecting BDNF-specific antibodies or control IgGs immediately at the time of L4-L6 spinal nerve injury, or in a delayed fashion one... (More)

Peripheral nerve injury results in dramatic upregulation in pituitary adenylate cyclase activating polypeptide (PACAP) expression in adult rat dorsal root ganglia and spinal motor neurons mirroring that described for the neurotrophin brain derived neurotrophic factor (BDNF). Thus, we posited that injury-associated alterations in BDNF expression regulate the changes in PACAP expression observed in the injured neurons. The role of endogenous BDNF in induction and/or maintenance of PACAP mRNA expression in injured adult rat motor and sensory neurons was examined by intrathecally infusing or intraperitoneally injecting BDNF-specific antibodies or control IgGs immediately at the time of L4-L6 spinal nerve injury, or in a delayed fashion one week later for 3 days followed by analysis of impact on PACAP expression. PACAP mRNA in injured lumbar sensory and motor neurons was detected using in situ hybridization, allowing quantification of relative changes between experimental groups, with ATF-3 immunofluorescence serving to identify the injured subpopulation of motor neurons. Both the incidence and level of PACAP mRNA expression were dramatically reduced in injured sensory and motor neurons in response to immediate intrathecal anti-BDNF treatment. In contrast, neither intraperitoneal injections nor delayed intrathecal infusions of anti-BDNF had any discernible impact on PACAP expression. This impact on PACAP expression in response to BDNF immunoneutralization in DRG was confirmed using qRT-PCR or by using BDNF selective siRNAs to reduce neuronal BDNF expression. Collectively, our findings support that endogenous injury-associated BDNF expression is critically involved in induction, but not maintenance, of injury-associated PACAP expression in sensory and motor neurons.

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published
subject
keywords
Animals, Antibody Specificity, Brain-Derived Neurotrophic Factor, Gene Expression Regulation, Male, Motor Neurons, Peripheral Nerve Injuries, Pituitary Adenylate Cyclase-Activating Polypeptide, RNA, Messenger, Rats, Sciatic Nerve, Sensory Receptor Cells
in
PLoS One
volume
9
issue
6
pages
100730 - 100730
publisher
Public Library of Science
external identifiers
  • Scopus:84903530281
ISSN
1932-6203
DOI
10.1371/journal.pone.0100730
language
English
LU publication?
no
id
43f02f36-2c53-4c2b-9d80-71804914892f
date added to LUP
2016-06-02 10:22:16
date last changed
2016-10-13 05:09:46
@misc{43f02f36-2c53-4c2b-9d80-71804914892f,
  abstract     = {<p>Peripheral nerve injury results in dramatic upregulation in pituitary adenylate cyclase activating polypeptide (PACAP) expression in adult rat dorsal root ganglia and spinal motor neurons mirroring that described for the neurotrophin brain derived neurotrophic factor (BDNF). Thus, we posited that injury-associated alterations in BDNF expression regulate the changes in PACAP expression observed in the injured neurons. The role of endogenous BDNF in induction and/or maintenance of PACAP mRNA expression in injured adult rat motor and sensory neurons was examined by intrathecally infusing or intraperitoneally injecting BDNF-specific antibodies or control IgGs immediately at the time of L4-L6 spinal nerve injury, or in a delayed fashion one week later for 3 days followed by analysis of impact on PACAP expression. PACAP mRNA in injured lumbar sensory and motor neurons was detected using in situ hybridization, allowing quantification of relative changes between experimental groups, with ATF-3 immunofluorescence serving to identify the injured subpopulation of motor neurons. Both the incidence and level of PACAP mRNA expression were dramatically reduced in injured sensory and motor neurons in response to immediate intrathecal anti-BDNF treatment. In contrast, neither intraperitoneal injections nor delayed intrathecal infusions of anti-BDNF had any discernible impact on PACAP expression. This impact on PACAP expression in response to BDNF immunoneutralization in DRG was confirmed using qRT-PCR or by using BDNF selective siRNAs to reduce neuronal BDNF expression. Collectively, our findings support that endogenous injury-associated BDNF expression is critically involved in induction, but not maintenance, of injury-associated PACAP expression in sensory and motor neurons.</p>},
  author       = {Pettersson, Lina M E and Geremia, Nicole M and Ying, Zhengxin and Verge, Valerie M K},
  issn         = {1932-6203},
  keyword      = {Animals,Antibody Specificity,Brain-Derived Neurotrophic Factor,Gene Expression Regulation,Male,Motor Neurons,Peripheral Nerve Injuries,Pituitary Adenylate Cyclase-Activating Polypeptide,RNA, Messenger,Rats,Sciatic Nerve,Sensory Receptor Cells},
  language     = {eng},
  number       = {6},
  pages        = {100730--100730},
  publisher    = {ARRAY(0x93667b0)},
  series       = {PLoS One},
  title        = {Injury-associated PACAP expression in rat sensory and motor neurons is induced by endogenous BDNF},
  url          = {http://dx.doi.org/10.1371/journal.pone.0100730},
  volume       = {9},
  year         = {2014},
}