Restricted diet rescues rat enteric motor neurones from age related cell death

Background-Alone among autonomic neurones, enteric neurones are known to be vulnerable to age related cell death; over 50% may be lost in aging rodent s. A previous study demonstrated unexpectedly that neurones of the myenteri c plexus from rats fed a restricted diet appeared not to suffer from extens ive cell death in contrast with previous studies of ad libitum fed animals. Aims-To compare myenteric neurone numbers in the ileum of young and aging m ale Sprague-Dawley rats fed either ad libitum or a restricted diet. Methods-Neurones were counted in whole mount preparations of rat ileum stai ned immunohistochemically for the pan-neuronal marker PGP9.5, for choline a cetyltransferase, or for nitric oxide synthase, or with NADH or NADPH histo chemistry. Results-Neurone numbers in the rat myenteric plexus were substantially affe cted by the dietary regimen: ad libitum feeding (50-60 g per day of standar d rat chow) resulted in the death of about 50% of myenteric neurones in 24 month Sprague-Dawley rats, while numbers were unchanged when the daily diet ary intake was halved between the ages of six and 24 months. Animals fed a double restricted diet (15 g per day) showed no cell loss at 30 months, as well as the predicted increase in longevity. Neurone loss was largely compl ete by 16 months in ad libitum fed animals. Numbers of cholinergic (possibl y motor) neurones, as demonstrated by choline acetyltransferase immunohisto chemistry, were substantially reduced in ad libitum fed aging rats but not in animals fed a restricted diet. Loss of cholinergic neurones after ad lib itum feeding was confirmed by reduced numbers of neurones of a size range m atching that of cholinergic neurones. Conclusions-Ad libitum feeding of adult rats has adverse effects on the sur vival of myenteric neurones, neurone loss commencing before 16 months of ag e. Cholinergic neurones appear to be particularly vulnerable to the effects of diet. Restricting dietary intake from six months of age prevents neuron e loss almost entirely up to 30 months of age in these rats.