5月7日担当の薬理学講座の川村です。
以下の論文を紹介いたします。
Hao Wen, Nagisa Sada, Tsuyoshi Inoue
Abstract
The ketogenic diet increases ketone bodies (β-hydroxybutyrate and
acetoacetate) in the brain, and ameliorates epileptic seizures in vivo.
However, ketone bodies exert weak or no effects on electrical activity
in rodent hippocampal slices. Especially, it remains unclear what kinds
of conditions are required to strengthen the actions of ketone bodies in
hippocampal slices. In the present study, we examined the effects of
acetoacetate on hippocampal pyramidal cells in normal slices and
epileptiform slices of mice. By using patch-clamp recordings from CA1
pyramidal cells, we first confirmed that acetoacetate did not change the
membrane potentials and intrinsic properties of pyramidal cells in
normal slices. However, we found that acetoacetate weakened spontaneous
epileptiform bursts in pyramidal cells of epileptiform slices, which
were acutely induced by applying convulsants to normal slices.
Interestingly, acetoacetate did not change the frequency of the
epileptiform bursts, but attenuated individual epileptiform bursts. We
finally examined the effects of acetoacetate on excitatory synaptic
barrages during epileptiform activity, and found that acetoacetate
weakened epileptiform bursts by reducing synchronous synaptic inputs.
These results show that acetoacetate attenuated neuronal bursts in
epileptiform slices, but did not affect neuronal activity in normal
slices, which leads to seizure-selective actions of ketone bodies.