Turnover of extra-cellular glucose and lactate in the rat striatum estimated by equilibrium micro-dialysis

Introduction

Intercellular trafficking of substrates is essential to meet the energy demand of the brain. Accordingly, neuronal energy consumption may depend on trafficking of glucose and lactate through the brain intercellular space (ICS, about 18% of tissue) to neurons. We report here estimates of ICS steady state levels (C_ss) and the relative amounts of lactate or glucose (indicated here as R%) that diffuse via the ICS of the striatum of conscious and freely moving rats.

Methods

We applied equilibrium microdialysis (eMD), that is very slow microdialysis (100 nL = 0.1 μL.min⁻¹). eMD allows the estimation of C_ss and the turnover rates in the ICS. Various concentrations of lactate and glucose were continuously infused and measured in the perfusate with miniature bio-sensors. The difference between the amounts infused and collected per time unit reflects the sum of diffusion and consumption of the substrates in the ICS surrounding the eMD-probe. The cellular transporters of lactate and glucose are bi-directional, so the rate of disappearance is predominantly due to metabolism at steady state perfusion. Rats were provided with conventional micro-dialyses probes and studied at various days post-surgery. eMD, animals, surgery, sensors, equipment and probes were done as reported^{1, 2}.

Results

C_ss of glucose (n = 10) and lactate (n= 6) were measured up to 6 days following the implantation of the probe. The lowest levels (± SEM) of glucose were measured at days 2, 3 and 4 and were 0.35 ± 0.07, 0.18 ± 0.04 and 0.31 ± 0.05 mM, respectively. The lactate levels did not significantly vary over 4 days; these levels were at day 2, 3 and 4, 0.64 ± 0.03, 0.68 ± 0.03 and 0.58 ± 0.02 mM, respectively. At day 3 and 4 the turnover rates of glucose (n = 6) and lactate (n = 6) were estimated by infusing glucose (0.5, 1.0, 2.0, 2.5 or 5.0 mM) or lactate (1.5, 2.5, 3.0, 4.0 or 5.0 mM). At day 3 six rats were studied either with lactate (3 rats) or with glucose (3 rats); the same rats were studied next day, but now with the other substrate. The turnover rate of lactate was 0.13 ± 0.03 μMol/g/min and that of glucose 0.03 ± 0.01 ±Mol/g/min. R% is less than 10%.

Conclusions

The relative amount of glucose diffusing through the ICS is far smaller than that of lactate (<1% versus > 7% of total energy consumption) and are in line with ³ . Our data do not support the idea that the majority of brain energy need is provided by the glutamate-recycling shuttle, but they emphasize that lactate, rather than glucose, is the major trafficking energy substrate.