PMID- 31068076
OWN - NLM
STAT- MEDLINE
DCOM- 20200428
LR  - 20200601
IS  - 1552-6844 (Electronic)
IS  - 1545-9683 (Print)
IS  - 1545-9683 (Linking)
VI  - 33
IP  - 6
DP  - 2019 Jun
TI  - The Val66Met BDNF Polymorphism and Peripheral Nerve Injury: Enhanced Regeneration 
      in Mouse Met-Carriers Is Not Further Improved With Activity-Dependent Treatment.
PG  - 407-418
LID - 10.1177/1545968319846131 [doi]
AB  - Activity-dependent treatments to enhance peripheral nerve regeneration after 
      injury have shown great promise, and clinical trials implementing them have 
      begun. Success of these treatments requires activity-dependent release of 
      brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP) 
      in the bdnf gene known as Val66Met, which is found in nearly one third of the 
      human population, results in defective activity-dependent BDNF secretion and 
      could impact the effectiveness of these therapies. Here, we used a mouse model of 
      this SNP to test the efficacy of treadmill exercise in enhancing axon 
      regeneration in animals both heterozygous (V/M) and homozygous (M/M) for the SNP. 
      Axon regeneration was studied 4 weeks after complete transection and repair of 
      the sciatic nerve in both male and female animals, using both 
      electrophysiological and histological outcome measures. Regeneration was enhanced 
      significantly without treatment in V/M mice, compared with wild type (V/V) 
      controls. Unlike V/V mice, treatment of both V/M and M/M mice with treadmill 
      exercise did not result in enhanced regeneration. These results were 
      recapitulated in vitro using dissociated neurons containing the light-sensitive 
      cation channel, channelrhodopsin. Three days after plating, neurites of neurons 
      from V/M and M/M mice were longer than those of V/V neurons. In neurons from V/V 
      mice, but not those from V/M or M/M animals, longer neurites were found after 
      optogenetic stimulation. Taken together, Met-carriers possess an intrinsically 
      greater capacity to regenerate axons in peripheral nerves, but this cannot be 
      enhanced further by activity-dependent treatments.
FAU - McGregor, Claire E
AU  - McGregor CE
AD  - 1 Emory University School of Medicine, Atlanta, GA, USA.
FAU - Irwin, Allison M
AU  - Irwin AM
AD  - 1 Emory University School of Medicine, Atlanta, GA, USA.
FAU - English, Arthur W
AU  - English AW
AD  - 1 Emory University School of Medicine, Atlanta, GA, USA.
LA  - eng
GR  - R01 NS057190/NS/NINDS NIH HHS/United States
GR  - UL1 TR002378/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190508
PL  - United States
TA  - Neurorehabil Neural Repair
JT  - Neurorehabilitation and neural repair
JID - 100892086
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - *Axons
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Disease Models, Animal
MH  - Exercise Therapy
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Nerve Regeneration/*genetics
MH  - Optogenetics
MH  - Peripheral Nerve Injuries/*therapy
MH  - Polymorphism, Single Nucleotide
MH  - Sciatic Nerve/*injuries
PMC - PMC6571055
MID - NIHMS1526478
OTO - NOTNLM
OT  - BDNF
OT  - Val66Met
OT  - exercise
OT  - optogenetics
OT  - peripheral nerve injury
COIS- Conflict of Interest: none.
EDAT- 2019/05/10 06:00
MHDA- 2020/04/29 06:00
PMCR- 2020/06/01
CRDT- 2019/05/10 06:00
PHST- 2019/05/10 06:00 [pubmed]
PHST- 2020/04/29 06:00 [medline]
PHST- 2019/05/10 06:00 [entrez]
PHST- 2020/06/01 00:00 [pmc-release]
AID - 10.1177/1545968319846131 [doi]
PST - ppublish
SO  - Neurorehabil Neural Repair. 2019 Jun;33(6):407-418. doi: 
      10.1177/1545968319846131. Epub 2019 May 8.