Background: A beneficial memory effect of acute fornix deep brain stimulation (DBS) has been reported in clinical studies. The aim of this study was to investigate the acute changes in glucose metabolism induced by fornix DBS.
Methods: First, the Morris water maze test and novel object recognition memory test were used to confirm declined memory in aged mice (C57BL/6, 20-22 months old). Then, four groups of mice were used as follows: aged mice with stimulation (n = 12), aged mice with sham-stimulation (n = 8), adult mice (3-4 months old) with stimulation (n = 12), and adult mice with sham-stimulation (n = 8). Ipsilateral hippocampal glucose metabolism and glutamate levels were measured in vivo by microdialysis before, during, and after fornix DBS treatment. Histological staining was used to verify the localization of electrodes and mice with inaccurate placement were excluded from subsequent analyses. The effects of fornix DBS on extracellular glucose, lactate, pyruvate, and glutamate levels over time were analyzed by repeated-measures analysis of variance followed by Fisher's least significant difference post hoc test.
Results: The aged mice had a higher basal lactate/pyruvate ratio (LPR) and lactate/glucose ratio (LGR) than the adult mice (LPR: 0.34 ± 0.04 vs. 0.13 ± 0.02, t = 4.626, P < 0.0001; LGR: 6.06 ± 0.59 vs. 4.14 ± 0.36, t = 2.823, P < 0.01). Fornix DBS decreased the ipsilateral hippocampal pyruvate and lactate levels (P < 0.05), but the glucose levels were not obviously changed in aged mice. Similarly, the LGR and LPR also decreased in aged mice after fornix DBS treatment (P < 0.05). Glucose metabolism in adult mice was not significantly influenced by fornix DBS. In addition, fornix DBS significantly decreased the ipsilateral hippocampal extracellular levels of glutamate in aged mice (P < 0.05), while significant alterations were not found in the adult mice.
Conclusions: The present study provides experimental evidence that fornix DBS could significantly improve hippocampal glucose metabolism in aged mice by promoting cellular aerobic respiration activity.
穹窿急性电刺激对老龄小鼠海马葡萄糖代谢的影响研究摘要背景：既往临床研究发现穹窿脑深部电刺激（deep brain stimulation, DBS）可以改善阿尔茨海默病患者记忆功能。本研究拟探讨急性穹窿刺激对海马葡萄糖代谢的影响，为术中急性穹窿刺激改善记忆功能现象提供理论基础。 方法：研究应用老龄小鼠（C57BL/6，20-22月龄）作为记忆下降动物模型，首先应用Morris水迷宫实验和新物体识别实验验证老龄小鼠与成年小鼠（C57BL/6，3-4月龄）相比存在记忆功能下降；随后实验小鼠分为4组：老龄小鼠刺激组（n = 12），老龄小鼠假刺激组 (n = 8)，成年小鼠刺激组（n = 12）和成年小鼠假刺激组(n=8)，于左侧穹窿靶点植入DBS电极，并在刺激前、刺激中和刺激后应用在体微透析方式采集小鼠同侧海马透析液，检测透析液中葡萄糖及其代谢产物、谷氨酸的含量，并应用重复测量的方差分析进行统计比较，组织学检查发现电极刺激部位不准确的小鼠对应数据不纳入统计学分析。 结果：老龄小鼠海马乳酸/丙酮酸比值（LPR）和乳酸/葡萄糖比值(LGR)明显高于成年小鼠 (LPR: 0.34 ± 0.04 vs. 0.13 ± 0.02, t = 4.626, P<0.0001; LGR: 6.06 ± 0.59 vs. 4.14 ± 0.36, t = 2.823, P<0.01)。穹窿电刺激可以显著降低老龄小鼠海马内丙酮酸和乳酸水平 (P<0.05)，而对葡萄糖含量无显著影响，此外，老龄小鼠海马LGR和LPR因穹窿刺激而出现明显下降（P<0.05），而穹窿电刺激对小鼠海马的葡萄糖代谢水平无显著影响。此外，穹窿电刺激同样可以抑制老龄小鼠海马谷氨酸的释放 (P<0.05)，而对成年小鼠无明显影响。 结论：穹窿脑深部电刺激通过改善有氧呼吸活动提高了老龄小鼠海马的葡萄糖代谢水平，可能是术中急性刺激改善记忆功能的机制之一。.
Keywords: Deep Brain Stimulation; Fornix; Glucose Metabolism; Memory Decline.