Restricted diet rescues rat enteric motor neurones from age related cell death
Restricted diet rescues rat enteric motor neurones from age related cell death
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DOI：
10.1136/gut.47.5.653
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发表时间：
2000-11-01
期刊：
影响因子：
24.5
通讯作者：
Santer, RM
中科院分区：
文献类型：
--
作者：
Cowen, T;Johnson, RJR;Santer, RM
在自主神经元中，肠神经元是唯一易受年龄相关性细胞死亡影响的神经元，在啮齿类动物中超过50%的细胞死亡。先前的研究出乎意料地表明，与先前的随意喂养动物的研究相比，限制饮食大鼠的肌间神经丛神经元似乎没有遭受广泛的细胞死亡。目的-比较随意或限制饮食喂养的年轻和年老雄性Sprague-Dawley大鼠回肠中肌间神经元的数量。在大鼠回肠的整个安装制备物中对神经元进行计数，对泛神经元标记物PGP9.5、胆碱乙酰转移酶或一氧化氮合酶进行化学染色，结果-大鼠肌间神经丛中的神经元数量受到饮食方案的显著影响：自由采食饲喂（50-60 g/天的标准大鼠食物）导致24个月的Sprague-Dawley大鼠中约50%的肌间神经元死亡，而在6个月至24个月之间，每日膳食摄入量减半时，数量没有变化。喂食双重限制饮食（每天15克）的动物在30个月时没有细胞损失，以及预期的寿命增加。在自由采食的动物中，神经元损失在16个月时基本完成。胆碱乙酰转移酶免疫组织化学显示，在随意喂养的老龄大鼠中，胆碱能（可能是运动）神经元的数量大幅减少，但在限制饮食的动物中则不然。自由采食后胆碱能神经元的损失被证实的大小范围匹配的胆碱能neurones. Conclusions成年大鼠自由采食的神经元的数量减少对肌间神经元的生存有不良影响，神经元损失开始前16个月的年龄。胆碱能神经元似乎特别容易受到饮食的影响。在这些大鼠中，从6个月大开始限制饮食摄入可以防止神经元几乎完全丧失，直到30个月大。
Background-Alone among autonomic neurones, enteric neurones are known to be vulnerable to age related cell death; over 50% may be lost in aging rodents. A previous study demonstrated unexpectedly that neurones of the myenteric plexus from rats fed a restricted diet appeared not to suffer from extensive 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 male Sprague-Dawley rats fed either ad libitum or a restricted diet.Methods-Neurones were counted in whole mount preparations of rat ileum stained immunohistochemically for the pan-neuronal marker PGP9.5, for choline acetyltransferase, or for nitric oxide synthase, or with NADH or NADPH histochemistry.Results-Neurone numbers in the rat myenteric plexus were substantially affected by the dietary regimen: ad libitum feeding (50-60 g per day of standard 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 dietary 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 complete by 16 months in ad libitum fed animals. Numbers of cholinergic (possibly motor) neurones, as demonstrated by choline acetyltransferase immunohistochemistry, were substantially reduced in ad libitum fed aging rats but not in animals fed a restricted diet. Loss of cholinergic neurones after ad libitum feeding was confirmed by reduced numbers of neurones of a size range matching that of cholinergic neurones.Conclusions-Ad libitum feeding of adult rats has adverse effects on the survival of myenteric neurones, neurone loss commencing before 16 months of age. Cholinergic neurones appear to be particularly vulnerable to the effects of diet. Restricting dietary intake from six months of age prevents neurone loss almost entirely up to 30 months of age in these rats.