β-hydroxybutyrate fuels synaptic function during development -: Histological and physiological evidence in rat hippocampal slices
β-hydroxybutyrate fuels synaptic function during development -: Histological and physiological evidence in rat hippocampal slices
复制标题
DOI：
10.1172/jci1009
复制
发表时间：
1998-03-01
影响因子：
15.9
通讯作者：
Zorumski, CF
中科院分区：
文献类型：
--
作者：
Izumi, Y;Ishii, K;Zorumski, CF
为了确定酮体是否维持神经元功能作为能量底物，我们研究了对羟基丁酸酯（PHB）对大鼠海马脑片葡萄糖剥夺过程中突触传递和形态完整性的影响。通过60分钟的葡萄糖剥夺抑制兴奋性突触后电位（EPSP）后，给予0.5-10 mM D-β HB恢复了出生后第15天（PND）大鼠脑片中的EPSP，但在PND 30或120大鼠脑片中没有恢复。在PND 15，向培养基中添加D-β HB允许由高频刺激触发的EPSP的鲁棒的长时程增强，并且阻止提示神经元过度兴奋的EPSP-尖峰易化。即使在PND 15之后，D-β HB也阻断由葡萄糖剥夺或糖酵解抑制产生的形态学变化。这些结果表明，D-β HB不仅能够取代葡萄糖作为能量底物，而且还能够保持神经元的完整性和稳定性，特别是在早期发育期间。
To determine whether ketone bodies sustain neuronal function as energy substrates, we examined the effects of P-hydroxybutyrate (PHB) 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-beta HB 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-beta HB 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-beta HB blocked morphological changes produced by either glucose deprivation or glycolytic inhibition. These results indicate that D-beta HB 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.