Izumi Y, Ishii K, Katsuki H, Benz A M, Zorumski C F
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Clin Invest. 1998 Mar 1;101(5):1121-32. doi: 10.1172/JCI1009.
To determine whether ketone bodies sustain neuronal function as energy substrates, we examined the effects of beta-hydroxybutyrate (betaHB) on synaptic transmission and morphological integrity during glucose deprivation in rat hippocampal slices. After the depression of excitatory postsynaptic potentials (EPSPs) by 60 min of glucose deprivation, administration of 0.5-10 mM D-betaHB restored EPSPs in slices from postnatal day (PND) 15 rats but not in slices from PND 30 or 120 rats. At PND 15, adding D-betaHB to the media allowed robust long-term potentiation of EPSPs triggered by high frequency stimulation, and prevented the EPSP-spike facilitation that suggests hyperexcitability of neurons. Even after PND 15,D-betaHB blocked morphological changes produced by either glucose deprivation or glycolytic inhibition. These results indicate that D-betaHB is not only able to substitute for glucose as an energy substrate but is also able to preserve neuronal integrity and stability, particularly during early development.
为了确定酮体是否作为能量底物维持神经元功能，我们研究了β-羟基丁酸（βHB）对大鼠海马切片葡萄糖剥夺期间突触传递和形态完整性的影响。在通过60分钟的葡萄糖剥夺使兴奋性突触后电位（EPSP）降低后，给予0.5-10 mM D-βHB可恢复出生后第15天（PND）大鼠切片中的EPSP，但不能恢复PND 30或120大鼠切片中的EPSP。在PND 15时，向培养基中添加D-βHB可使高频刺激触发的EPSP产生强大的长期增强作用，并防止提示神经元过度兴奋的EPSP-峰电位易化。即使在PND 15之后，D-βHB也能阻止由葡萄糖剥夺或糖酵解抑制所产生的形态学变化。这些结果表明，D-βHB不仅能够替代葡萄糖作为能量底物，而且还能够维持神经元的完整性和稳定性，尤其是在早期发育期间。
