Thrasivoulou, C.; Soubeyre, V.; Ridha, H.; Giuliani, D.; Giaroni, C.; Michael, G.J.; Saffrey, M.J. and Cowen, T.
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|DOI (Digital Object Identifier) Link:||http://dx.doi.org/10.1111/j.1474-9726.2006.00214.x|
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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, ihydrorhodamine (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.
|Item Type:||Journal Article|
|Extra Information:||Some of the symbols may not have transferred correctly into this bibliographic record.|
|Keywords:||aging; ageing; antioxidant defence; apoptosis; cell death; dietary restriction; myenteric neurons; neurotrophic factors; reactive oxygen species|
|Academic Unit/Department:||Science > Life, Health and Chemical Sciences
|Interdisciplinary Research Centre:||Biomedical Research Network (BRN)|
|Depositing User:||Jill Saffrey|
|Date Deposited:||29 Aug 2006|
|Last Modified:||14 Jan 2016 16:12|
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Reactive oxygen species, dietary restriction and neurotrophic factors in age-related loss of myenteric neurons. (deposited 14 Nov 2006)
- Reactive oxygen species, dietary restriction and neurotrophic factors in age-related loss of myenteric neurons. (deposited 29 Aug 2006) [Currently Displayed]