Long-Term Caloric Restriction Prevents Aging-Related Degeneration of Submucosal Neurons in Murine Small Intestine

R.A. Reddix*, D. Meyn, X. Cao and Q. Ma

Department of Pharmacology & Experimental Therapeutics
MEB 7110
LSUHSC
1901 Perido St.
New Orleans, LA 70112




LONG-TERM CALORIC RESTRICTION PREVENTS AGING-RELATED DEGENERATION OF SUBMUCOSAL NEURONS IN MURINE SMALL INTESTINE.
R.A. Reddix, D. Meyn, X. Cao, and Q. Ma. Department of Pharmacology & Experimental Therapeutics, LSUHSC, New Orleans, LA 70112
Background: It was previously shown that caloric restriction (CR) is neuroprotective in the central nervous system and retards the neurodegenerative process in models of Alzheimer’s disease and Parkinson’s disease. Aim: To determine whether long-term caloric restriction is neuroprotective in the enteric nervous system of murine small intestine. In addition, to determine whether the neuroprotection is associated with changes in the expression of glial cell-derived neurotrophic factor (GDNF). Methods: This study was carried out in two phases. Phase 1 we examined histochemical changes in cholinergic submucous neurons by monitoring choline acetylcholine transferase (CHAT) staining. We also employed immunohistochemical staining and western blot analysis to assess changes in GDNF expression during aging. Phase 2 we examined the effect of long-term CR on age-related changes in both cholinergic neurons and GDNF expression within submucous ganglia. Experimental groups: young (3-4 month) and old (18-20 month) C57BL/6 mice; ad lib and CR, 20 month C57BL/6 mice. Results: Our results showed degeneration of CHAT positive neurons and an age-related decline in GDNF-immunoreactivity (IR) within the small intestine of old mice. Moreover, we identified a 21kDa GDNF-IR band in ganglia isolated from all animals. The density of GDNF-IR bands were decreased with age. Long-Term CR prevented the degeneration of cholinergic neurons and the decline in GDNF expression within the submucous ganglia of old mice. Conclusion: The results suggest that long-term CR is neuroprotective in submucous ganglia of old mice. The neuroprotective effects may be partially mediated by an increase in GDNF expression. Supported by NIA grant, AG 18600-01




Key words: Caloric restriction, Aging, enteric nervous system, glial cell-derived neurotrophic factor

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