Effect of ketone body (d-3-hydroxybutyrate) on neural activity and energy metabolism in hippocampal slices of the adult guinea pig

Abstract The role of ketone bodyon neural activity and energy metabolism in the brain was investigated. Guinea pig hippocampal sliceswere prepared, and postsynaptic field potentials (PSPs) were recorded in the granular cell layer of the dentate gyrus. ATP and phosphocreatine(CrP) in the tissue slicewere measured after 60 and 120 min incubation in standard medium (1) with 10 mM glucose, (2) with 10 mM glucose plus 20 mM d,l -3-hydroxybutyrate (3-OHBA), (3) without glucose, (4) with 20 mM 3-OHBA instead of 10 mM glucose. In (3), both ATP and CrP in the slicedecreased to 40–45% of the original level after 120 min. On the other hand, the ATP level was well maintained even 120 min after incubation in (1), (2) and (4), whereas the CrP level decreased to 62% in (4). Further, sliceswere incubated in (3) and (4) for 30, 60, and 120 min, and the presence of PSP was tested. In (3), the number of slicesfrom which PSPs could be recorded decreased, and after 120 min PSPs were hardly observed. In (4), that number decreased gradually, and only 45% of the slicesshowed PSPs after 120 min. These results indicate that 3-OHBA can be a substrate to produce high-energy phosphatebut cannot maintain the neural activity as glucose does.