PMID- 12573513
OWN - NLM
STAT- MEDLINE
DCOM- 20030418
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 964
IP  - 1
DP  - 2003 Feb 21
TI  - Enhancement of BDNF and activated-ERK immunoreactivity in spinal motor neurons 
      after peripheral administration of BDNF.
PG  - 56-66
AB  - Brain-derived neurotrophic factor (BDNF) shows neurotrophic effects on adult 
      motor neurons when given systemically, But it is unknown whether systemically 
      administered BDNF is transported to central cell bodies to affect them directly. 
      Here we used immunohistochemistry to investigate the transport of peripherally 
      injected BDNF to spinal motor neurons and the subsequent activation of a 
      signaling pathway. We first injected BDNF into the flexor digitorum brevis (FDB) 
      and analyzed the motor nucleus that projects to the FDB for BDNF immunoreactivity 
      (BDNF-ir) and phosphorylated extracellular signal-regulated kinase (ERK) 1/2 
      immunoreactivity (pERK1/2-ir). Both immunoreactivities were observed in the motor 
      neuron cell bodies. Next, BDNF was injected subcutaneously (s.c.) into rats with 
      a unilaterally axotomized sciatic nerve. pERK1/2-ir was detected in motor neurons 
      of the lesioned side. BDNF-ir and pERK1/2-ir were also observed on the unlesioned 
      side when a high dose of BDNF was injected. Therefore, we examined BDNF-ir and 
      pERK1/2-ir after injecting BDNF s.c. into normal rats. Both immunoreactivities 
      were observed in motor nuclei on both sides. Finally, we examined pERK1/2-ir 
      after a lower dose of BDNF was injected, which prevents the decrease in choline 
      acetyl transferase that occurs in the motor neuron upon axotomy. Spinal motor 
      nuclei contained a few cell bodies with pERK1/2-ir. These findings represent the 
      first direct evidence that subcutaneously injected BDNF is transported to motor 
      neurons and that it activates a signaling pathway in the spinal cord and exhibits 
      neurotrophic effects in vivo.
FAU - Kishino, Akiyoshi
AU  - Kishino A
AD  - Sumitomo Pharmaceuticals Research Division, 3-1-98 Kasugadenaka, Konohana-ku, 
      Osaka 554-0022, Japan. kishino@sumitomopharm.co.jp
FAU - Nakayama, Chikao
AU  - Nakayama C
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Anterior Horn Cells/*drug effects/metabolism
MH  - Axonal Transport/*drug effects/physiology
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Functional Laterality/drug effects/physiology
MH  - Immunohistochemistry
MH  - Injections, Intramuscular
MH  - MAP Kinase Signaling System/drug effects/physiology
MH  - Male
MH  - Mitogen-Activated Protein Kinases/drug effects/*metabolism
MH  - Motor Neuron Disease/drug therapy/metabolism/physiopathology
MH  - Muscle, Skeletal/*innervation
MH  - Nerve Regeneration/drug effects/physiology
MH  - Peripheral Nervous System Diseases/drug therapy/metabolism/physiopathology
MH  - Presynaptic Terminals/*drug effects/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reaction Time/drug effects/physiology
MH  - Up-Regulation/*drug effects/physiology
EDAT- 2003/02/08 04:00
MHDA- 2003/04/19 05:00
CRDT- 2003/02/08 04:00
PHST- 2003/02/08 04:00 [pubmed]
PHST- 2003/04/19 05:00 [medline]
PHST- 2003/02/08 04:00 [entrez]
AID - S0006899302040660 [pii]
AID - 10.1016/s0006-8993(02)04066-0 [doi]
PST - ppublish
SO  - Brain Res. 2003 Feb 21;964(1):56-66. doi: 10.1016/s0006-8993(02)04066-0.