PMID- 16842497
OWN - NLM
STAT- MEDLINE
DCOM- 20060905
LR  - 20131121
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 5
IP  - 3
DP  - 2006 Jun
TI  - Reactive oxygen species, dietary restriction and neurotrophic factors in 
      age-related loss of myenteric neurons.
PG  - 247-57
AB  - We have studied the mechanisms underlying nonpathological age-related neuronal 
      cell death. Fifty per cent of neurons in the rat enteric nervous system are lost 
      between 12 and 18 months of age in ad libitum (AL) fed rats. Caloric restriction 
      (CR) protects almost entirely against this neuron loss. Using the ROS-sensitive 
      dyes, dihydrorhodamine (DHR) and 
      2-[6-(4'-hydroxy)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid (HPF) in vitro, we 
      show that the onset of cell death is linked with elevated intraneuronal levels of 
      reactive oxygen species (ROS). Treatment with the neurotrophic factors NT3 and 
      GDNF enhances neuronal antioxidant defence in CR rats at 12-15 months and 24 
      months but not in adult or aged AL-fed animals. To examine the link between 
      elevated ROS and neuronal cell death, we assessed apoptotic cell death following 
      in vitro treatment with the redox-cycling drug, menadione. Menadione fails to 
      increase apoptosis in 6-month neurons. However, in 12-15mAL fed rats, when 
      age-related cell death begins, menadione induces a 7- to 15-fold increase in the 
      proportion of apoptotic neurons. CR protects age-matched neurons against 
      ROS-induced apoptosis. Treatment with neurotrophic factors, in particular GDNF, 
      rescues neurons from menadione-induced cell death, but only in 12-15mCR animals. 
      We hypothesize that CR enhances antioxidant defence through neurotrophic factor 
      signalling, thereby reducing age-related increases in neuronal ROS levels and in 
      ROS-induced cell death.
FAU - Thrasivoulou, C
AU  - Thrasivoulou C
AD  - Department of Anatomy and Developmental Biology, University College London, Royal 
      Free Campus, London NW3 2PF, UK.
FAU - Soubeyre, V
AU  - Soubeyre V
FAU - Ridha, H
AU  - Ridha H
FAU - Giuliani, D
AU  - Giuliani D
FAU - Giaroni, C
AU  - Giaroni C
FAU - Michael, G J
AU  - Michael GJ
FAU - Saffrey, M J
AU  - Saffrey MJ
FAU - Cowen, T
AU  - Cowen T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Antioxidants)
RN  - 0 (Calbindin 2)
RN  - 0 (Calbindins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (S100 Calcium Binding Protein G)
SB  - IM
EIN - Aging Cell. 2006 Aug;5(4):359
MH  - Aging/*physiology
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Calbindin 2
MH  - Calbindins
MH  - *Caloric Restriction
MH  - Cell Death/drug effects
MH  - Male
MH  - Myenteric Plexus/cytology/*drug effects
MH  - Nerve Growth Factors/*pharmacology
MH  - Neurons/cytology/*drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/*metabolism/pharmacology
MH  - S100 Calcium Binding Protein G/metabolism
EDAT- 2006/07/18 09:00
MHDA- 2006/09/06 09:00
CRDT- 2006/07/18 09:00
PHST- 2006/07/18 09:00 [pubmed]
PHST- 2006/09/06 09:00 [medline]
PHST- 2006/07/18 09:00 [entrez]
AID - ACE214 [pii]
AID - 10.1111/j.1474-9726.2006.00214.x [doi]
PST - ppublish
SO  - Aging Cell. 2006 Jun;5(3):247-57. doi: 10.1111/j.1474-9726.2006.00214.x.