11月11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。

Ketogenic Diet Dampens Excitatory Neurotransmission by Shrinking
Synaptic Vesicle Pools

Marion I. Stunault, Pan-Yue Deng, Anjali Yadav, Erica M. Periandri,
Francisca N. de Luna Vitorino, Michael B. Thomsen, Jasmin Sponagel,
Amelia J. Barfield, Renzelle J. Ponce, Layla Foroughi, Benjamin A.
Garcia, Gabor Egervari, Vitaly A. Klyachko, Ghazaleh Ashrafi

Cell Reports 45, 116945 (2026)

Abstract

Ketogenic diet (KD) is used for the treatment of drug-resistant
childhood epilepsy and has been proposed to improve outcomes in
neurodegenerative diseases. However, the mechanisms by which KD alters
brain circuitry remain unclear. Here, we investigated the impact of KD
on hippocampal function through integrative analysis of gene expression
and neurotransmission. We found that KD induces extensive
transcriptional reprogramming, including altered expression of numerous
synaptic genes. Proteomic and genomic profiling revealed significant
changes in histone modifications, particularly at promoters of
KD-regulated genes. Electrophysiological recordings showed that KD
reduces excitatory synaptic gain and short-term plasticity at CA3-CA1
synapses, dampening the summation of excitatory inputs and enhancing the
summation of inhibitory inputs. These functional changes were driven, in
part, by a reduction in the readily releasable vesicle pool at
excitatory synapses under KD. Together, our findings demonstrate that KD
drives transcriptional remodeling of hippocampal circuits, leading to
synaptic adaptations that may underlie its anti-epileptic and
neuroprotective effects.

何卒よろしくお願いいたします。
薬理学講座　川村将仁