Balietti Marta, Giorgetti Belinda, Fattoretti Patrizia, Grossi Yessica, Di Stefano Giuseppina, Casoli Tiziana, Platano Daniela, Solazzi Moreno, Orlando Fiorenza, Aicardi Giorgio, Bertoni-Freddari Carlo
Neurobiology of Aging Laboratory, INRCA Research Department, Ancona, Italy.
Rejuvenation Res. 2008 Jun;11(3):631-40. doi: 10.1089/rej.2007.0650.
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(s) and Nv(m)) 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.
生酮饮食（KDs）对多种疾病具有有益作用，如癫痫、线粒体病、癌症和神经退行性疾病。然而，人们对其对衰老个体的影响知之甚少。在本研究中，对19月龄的成年晚期大鼠喂食两种中链甘油三酯（MCT）-KDs 8周，并在海马CA1区分子层（SM CA1）和海马齿状回外分子层（OML DG）评估以下反映突触可塑性的形态学参数：突触的平均面积（S）、数量密度（Nv(s)）和表面密度（Sv），以及突触线粒体的平均体积（V）、数量密度（Nv(m)）和体积密度（Vv）。在SM CA1中，MCT-KDs诱导了老年动物典型形态模式的早期出现（较高的S和V，以及较低的Nv(s)和Nv(m)）。相反，在OML DG中，与对照组相比，喂食MCT-KDs的大鼠的Sv和Vv更高（由于较高的Nv(s)和Nv(m)）；已知这些改变可改善突触功能和代谢供应。MCT-KDs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 CA1更不易受影响，并且酮体摄取和分解代谢的重新激活可能在该区域更有效地发生，从而使其能够利用其独特的代谢特性。目前的研究结果提供了首个证据，表明MCT-KDs可能会引起相反的形态学改变，对SM CA1可能有潜在危害，而对OML DG可能有潜在益处。这意味着在衰老过程中其治疗应用存在风险，但也有令人期待的潜力。
