PMID- 24013014
OWN - NLM
STAT- MEDLINE
DCOM- 20131209
LR  - 20231213
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 249
DP  - 2013 Nov
TI  - Sympathetic denervation of peri-infarct myocardium requires the p75 neurotrophin 
      receptor.
PG  - 111-9
LID - S0014-4886(13)00255-0 [pii]
LID - 10.1016/j.expneurol.2013.08.015 [doi]
AB  - Development of cardiac sympathetic heterogeneity after myocardial infarction 
      contributes to ventricular arrhythmias and sudden cardiac death. Regions of 
      sympathetic hyperinnervation and denervation appear in the viable myocardium 
      beyond the infarcted area. While elevated nerve growth factor (NGF) is implicated 
      in sympathetic hyperinnervation, the mechanisms underlying denervation are 
      unknown. Recent studies show that selective activation of the p75 neurotrophin 
      receptor (p75(NTR)) in sympathetic neurons causes axon degeneration. We used mice 
      that lack p75(NTR) to test the hypothesis that activation of p75(NTR) causes 
      peri-infarct sympathetic denervation after cardiac ischemia-reperfusion. Wild 
      type hearts exhibited sympathetic denervation adjacent to the infarct 24h and 3 
      days after ischemia-reperfusion, but no peri-infarct sympathetic denervation 
      occurred in p75(NTR)-/- mice. Sympathetic hyperinnervation was found in the 
      distal peri-infarct myocardium in both genotypes 3 days after MI, and 
      hyperinnervation was increased in the p75(NTR)-/- mice. By 7 days after 
      ischemia-reperfusion, cardiac sympathetic innervation density returned back to 
      sham-operated levels in both genotypes, indicating that axonal pruning did not 
      require p75(NTR). Prior studies revealed that proNGF is elevated in the damaged 
      left ventricle after ischemia-reperfusion, as is mRNA encoding brain-derived 
      neurotrophic factor (BDNF). ProNGF and BDNF preferentially bind p75(NTR) rather 
      than TrkA on sympathetic neurons. Immunohistochemistry using Bdnf-HA mice 
      confirmed the presence of BDNF or proBDNF in the infarct after 
      ischemia-reperfusion. Thus, at least two p75(NTR) ligands are elevated in the 
      left ventricle after ischemia-reperfusion where they may stimulate 
      p75(NTR)-dependent denervation of peri-infarct myocardium. In contrast, 
      NGF-induced sympathetic hyperinnervation in the distal peri-infarct ventricle is 
      attenuated by p75(NTR).
CI  - (c) 2013.
FAU - Lorentz, Christina U
AU  - Lorentz CU
AD  - Department of Physiology and Pharmacology, Oregon Health and Science University, 
      3181 SW Sam Jackson Park Rd. Portland, OR 97239, USA.
FAU - Parrish, Diana C
AU  - Parrish DC
FAU - Alston, Eric N
AU  - Alston EN
FAU - Pellegrino, Michael J
AU  - Pellegrino MJ
FAU - Woodward, William R
AU  - Woodward WR
FAU - Hempstead, Barbara L
AU  - Hempstead BL
FAU - Habecker, Beth A
AU  - Habecker BA
LA  - eng
GR  - HL093056/HL/NHLBI NIH HHS/United States
GR  - R01 NS064114/NS/NINDS NIH HHS/United States
GR  - R01 HL093056/HL/NHLBI NIH HHS/United States
GR  - R01 NS030687/NS/NINDS NIH HHS/United States
GR  - NS064114/NS/NINDS NIH HHS/United States
GR  - NS030687/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130903
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Ngfr protein, mouse)
SB  - IM
MH  - Animals
MH  - Female
MH  - Heart Injuries/*metabolism/pathology
MH  - Heart Ventricles/*innervation/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocardial Infarction/*metabolism/pathology
MH  - Myocardium/*metabolism/pathology
MH  - Receptors, Nerve Growth Factor/*deficiency
MH  - Sympathectomy/*methods
PMC - PMC3826885
MID - NIHMS526273
OTO - NOTNLM
OT  - 123I-MIBG
OT  - Axon degeneration
OT  - BDNF
OT  - Brain-derived neurotrophic factor
OT  - HA
OT  - Ischemia-reperfusion
OT  - LAD
OT  - MI
OT  - NE
OT  - NGF
OT  - Pruning
OT  - Regeneration
OT  - SCG
OT  - TH
OT  - TrkA
OT  - brain-derived neurotrophic factor
OT  - hemagglutinin
OT  - iodine-123 meta-iodobenzylguanidine
OT  - left anterior descending coronary artery
OT  - myocardial infarction
OT  - nerve growth factor
OT  - norepinephrine
OT  - p75 neurotrophin receptor
OT  - p75(NTR)
OT  - superior cervical ganglia
OT  - tropomyosin-related receptor kinase A
OT  - tyrosine hydroxylase
EDAT- 2013/09/10 06:00
MHDA- 2013/12/16 06:00
PMCR- 2014/11/01
CRDT- 2013/09/10 06:00
PHST- 2013/04/16 00:00 [received]
PHST- 2013/08/23 00:00 [revised]
PHST- 2013/08/27 00:00 [accepted]
PHST- 2013/09/10 06:00 [entrez]
PHST- 2013/09/10 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - S0014-4886(13)00255-0 [pii]
AID - 10.1016/j.expneurol.2013.08.015 [doi]
PST - ppublish
SO  - Exp Neurol. 2013 Nov;249:111-9. doi: 10.1016/j.expneurol.2013.08.015. Epub 2013 
      Sep 3.