Ketogenic diets cause opposing changes in synaptic morphology in CA1 hippocampus and dentate gyrus of late-adult rats
Ketogenic diets cause opposing changes in synaptic morphology in CA1 hippocampus and dentate gyrus of late-adult rats
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DOI：
10.1089/rej.2007.0650
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发表时间：
2008-06-01
影响因子：
2.6
通讯作者：
Bertoni-Freddari, Carlo
中科院分区：
文献类型：
--
作者：
Balietti, Marta;Giorgetti, Belinda;Bertoni-Freddari, Carlo
生酮饮食（KDs）对几种疾病，如癫痫、癫痫病、癌症和神经退行性疾病有有益的影响。然而，人们对它们对老年人的影响知之甚少。在本研究中，用两种中链甘油三酯（MCT）-KD喂养（19月龄）大鼠8周，评价海马CA 1区分子层（SM CA 1）和海马齿状回外分子层（OML DG）中反映突触可塑性的以下形态学参数：突触的平均面积（S）、数密度（Nv（s））和表面密度（Sv），以及突触线粒体的平均体积（V）、数密度（Nv（m））和体积密度（Vv）。在SM CA 1中，MCT-KD诱导早期出现老年动物的典型形态学模式（S和V较高，Nv（s）和Nv（m）较低）。相反，在OML DG中，喂食MCT-KD的大鼠的Sv和Vv高于对照组（由于Nv和Nvm较高）;已知这些修饰可改善突触功能和代谢供应。MCT-KD的相反作用可能反映了对衰老过程的不同易感性：OML DG比SM CA 1更不脆弱，并且在该区域可能更有效地重新激活酮体摄取和催化，从而可以利用其特有的代谢特性。目前的研究结果提供了第一个证据表明，MCT-KD可能会导致相反的形态学修饰，对SM CA 1可能有害，对OML DG可能有利。这意味着风险，但也有希望的潜力，他们的治疗用途在老化。
Ketogenic diets (KDs) have beneficial effects on several diseases, such as epilepsy, mitochondriopathies, cancer, and neurodegeneration. However, little is known about their effects on aging individuals. In the present study, late-adult (19-month-old) rats were fed for 8 weeks with two medium chain triglycerides (MCT)-KDs, and the following morphologic parameters reflecting synaptic plasticity were evaluated in stratum moleculare of hippocampal CA1 region (SM CA1) and outer molecular layer of hippocampal dentate gyrus (OML DG): average area (S), numeric density (Nv(s)), and surface density (Sv) of synapses, and average volume (V), numeric density (Nv(m)), and volume density (Vv) of synaptic mitochondria. In SM CA1, MCT-KDs induced the early appearance of the morphologic patterns typical of old animals (higher S and V, and lower Nv(s) and Nv(m)). On the contrary, in OML DG, Sv and Vv of MCT-KDs-fed rats were higher (as a result of higher Nv, and Nvm) versus controls; these modifications are known to improve synaptic function and metabolic supply. The opposite effects of MCT-KDs might reflect the different susceptibility to aging processes: OML DG is less vulnerable than SM CA1, and the reactivation of ketone bodies uptake and catabolism might occur more efficiently in this region, allowing the exploitation of their peculiar metabolic properties. Present findings provide the first evidence that MCT-KDs may cause opposite morphologic modifications, being potentially harmful for SM CA1 and potentially advantageous for OML DG. This implies risks but also promising potentialities for their therapeutic use during aging.