Acute Fornix Deep Brain Stimulation Improves Hippocampal Glucose Metabolism in Aged Mice

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.