PMID- 31192302
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 2376-7839 (Print)
IS  - 2376-7839 (Electronic)
IS  - 2376-7839 (Linking)
VI  - 5
IP  - 3
DP  - 2019 Jun
TI  - Brain-derived neurotrophic factor, epigenetics in stroke skeletal muscle, and 
      exercise training.
PG  - e331
LID - 10.1212/NXG.0000000000000331 [doi]
LID - e331
AB  - OBJECTIVE: (1) To compare paretic (P) vs nonparetic (NP) skeletal muscle 
      brain-derived neurotrophic factor (BDNF) and the effects of resistive training 
      (RT) on systemic and skeletal muscle BDNF mRNA expression in stroke; and (2) to 
      compare the DNA methylation profile for BDNF and BDNFAS (BDNF antisense RNA) 
      between P and NP muscle and the effects of aerobic exercise training (AEX) on DNA 
      methylation in stroke. METHODS: In this longitudinal investigation, participants 
      (50-76 years) with chronic stroke underwent a fasting blood draw, a 12-week 
      (3x/week) RT intervention (n = 16), and repeated bilateral vastus lateralis 
      muscle tissue biopsies (n = 10) with BDNF expression determined by RT-PCR. Five 
      stroke survivors completed 6 months of AEX (3x/week) and had bilateral muscle 
      biopsies. DNA methylation status in gene BDNF and BDNFAS was assessed by Illumina 
      450k methylation array. RESULTS: P muscle had  approximately 45% lower BDNF mRNA expression 
      than NP muscle (6.79 +/- 1.30 vs 10.52 +/- 2.06 arbitrary units [AU], p < 0.05), and 
      P muscle exhibited differential methylation status in the DNA sequences of BDNF 
      (3 CpG [5'-C-phosphate-G-3'] sites, p = 0.016-0.044) and BDNFAS (1 CpG site, p = 
      0.016) compared to NP. Plasma BDNF and muscle BDNF messenger RNA (mRNA) 
      expression did not significantly change after RT. BDNFAS DNA methylation 
      increased after AEX in P relative to NP muscle (p = 0.017). CONCLUSIONS: This is 
      the first evidence that stroke hemiparesis reduces BDNF skeletal muscle 
      expression, with our findings identifying methylation alterations on the DNA 
      sequence of BDNF and BDNFAS gene. Preliminary results further indicate that AEX 
      increases methylation in BDNFAS gene, which presumably could regulate the 
      expression of BDNF.
FAU - Ryan, Alice S
AU  - Ryan AS
AD  - VA Maryland Health Care System, Research Service, Department of Medicine, 
      Division of Gerontology and Geriatric Medicine, Department of Neurology, at the 
      University of Maryland School of Medicine, and the Baltimore Geriatric Research, 
      Education and Clinical Center (GRECC), MD.
FAU - Xu, Huichun
AU  - Xu H
AD  - VA Maryland Health Care System, Research Service, Department of Medicine, 
      Division of Gerontology and Geriatric Medicine, Department of Neurology, at the 
      University of Maryland School of Medicine, and the Baltimore Geriatric Research, 
      Education and Clinical Center (GRECC), MD.
FAU - Ivey, Frederick M
AU  - Ivey FM
AD  - VA Maryland Health Care System, Research Service, Department of Medicine, 
      Division of Gerontology and Geriatric Medicine, Department of Neurology, at the 
      University of Maryland School of Medicine, and the Baltimore Geriatric Research, 
      Education and Clinical Center (GRECC), MD.
FAU - Macko, Richard F
AU  - Macko RF
AD  - VA Maryland Health Care System, Research Service, Department of Medicine, 
      Division of Gerontology and Geriatric Medicine, Department of Neurology, at the 
      University of Maryland School of Medicine, and the Baltimore Geriatric Research, 
      Education and Clinical Center (GRECC), MD.
FAU - Hafer-Macko, Charlene E
AU  - Hafer-Macko CE
AD  - VA Maryland Health Care System, Research Service, Department of Medicine, 
      Division of Gerontology and Geriatric Medicine, Department of Neurology, at the 
      University of Maryland School of Medicine, and the Baltimore Geriatric Research, 
      Education and Clinical Center (GRECC), MD.
LA  - eng
GR  - P30 AG028747/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20190501
PL  - United States
TA  - Neurol Genet
JT  - Neurology. Genetics
JID - 101671068
PMC - PMC6515940
EDAT- 2019/06/14 06:00
MHDA- 2019/06/14 06:01
PMCR- 2019/05/01
CRDT- 2019/06/14 06:00
PHST- 2019/01/24 00:00 [received]
PHST- 2019/03/25 00:00 [accepted]
PHST- 2019/06/14 06:00 [entrez]
PHST- 2019/06/14 06:00 [pubmed]
PHST- 2019/06/14 06:01 [medline]
PHST- 2019/05/01 00:00 [pmc-release]
AID - NG2019010058 [pii]
AID - 10.1212/NXG.0000000000000331 [doi]
PST - epublish
SO  - Neurol Genet. 2019 May 1;5(3):e331. doi: 10.1212/NXG.0000000000000331. 
      eCollection 2019 Jun.