Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China.
Stereotactic and Functional Neurosurgery Laboratory, Beijing Neurosurgical Institute, Capital Medical University; Beijing Key Laboratory of Neurostimulation, Beijing 100050, China.
Chin Med J (Engl). 2018 Mar 5;131(5):594-599. doi: 10.4103/0366-6999.226067.
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.
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.
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.
The present study provides experimental evidence that fornix DBS could significantly improve hippocampal glucose metabolism in aged mice by promoting cellular aerobic respiration activity.
临床研究报道了穹窿深部脑刺激（DBS）的有益记忆效应。本研究旨在探讨穹窿 DBS 诱导的急性葡萄糖代谢变化。
首先，使用 Morris 水迷宫测试和新物体识别记忆测试确认了老年小鼠（C57BL/6，20-22 月龄）的记忆减退。然后，将 4 组小鼠分为以下几组：刺激的老年小鼠（n = 12）、假刺激的老年小鼠（n = 8）、刺激的成年小鼠（3-4 月龄）（n = 12）和假刺激的成年小鼠（n = 8）。在穹窿 DBS 治疗前、治疗中和治疗后，通过微透析测量同侧海马的葡萄糖代谢和谷氨酸水平。组织学染色用于验证电极的定位，将位置不准确的小鼠排除在后续分析之外。通过重复测量方差分析和 Fisher 的最小显著差异事后检验分析穹窿 DBS 对细胞外葡萄糖、乳酸、丙酮酸和谷氨酸水平随时间的影响。
老年小鼠的基础乳酸/丙酮酸比值（LPR）和乳酸/葡萄糖比值（LGR）高于成年小鼠（LPR：0.34 ± 0.04 比 0.13 ± 0.02，t = 4.626，P < 0.0001；LGR：6.06 ± 0.59 比 4.14 ± 0.36，t = 2.823，P < 0.01）。穹窿 DBS 降低了同侧海马的丙酮酸和乳酸水平（P < 0.05），但老年小鼠的葡萄糖水平没有明显变化。同样，穹窿 DBS 治疗后老年小鼠的 LGR 和 LPR 也降低（P < 0.05）。穹窿 DBS 对成年小鼠的葡萄糖代谢没有显著影响。此外，穹窿 DBS 显著降低了老年小鼠同侧海马的细胞外谷氨酸水平（P < 0.05），而成年小鼠则没有明显变化。
本研究提供了实验证据，表明穹窿 DBS 通过促进细胞有氧呼吸活动，可显著改善老年小鼠海马的葡萄糖代谢。
