2023-10-05 カリフォルニア大学サンディエゴ校(UCSD)
◆コカイン中毒は分子レベルで理解が不足しており、承認された薬物治療がほとんどないため、この研究は重要です。杏仁体の細胞ごとの解析から、エネルギー代謝と中毒行動の関連が示唆され、中毒行動を逆転させる薬物がテストされました。
◆今後は、大規模なサンプルサイズの研究を進め、遺伝子とコカインの使用に対する反応の相互作用を理解し、中毒の個別リスクを明らかにすることが目指されています。
<関連情報>
- https://today.ucsd.edu/story/cellular-atlas-of-amygdala-reveals-new-treatment-target-for-cocaine-addiction
- https://www.nature.com/articles/s41593-023-01452-y
コカイン中毒様行動の異なる近交系ラットにおける単一核ゲノム解析により、遺伝子扁桃体GABA作動性抑制の変化が明らかになった。 Single-nucleus genomics in outbred rats with divergent cocaine addiction-like behaviors reveals changes in gene amygdala GABAergic inhibition
Jessica L. Zhou,Giordano de Guglielmo,Aaron J. Ho,Marsida Kallupi,Narayan Pokhrel,Hai-Ri Li,Apurva S. Chitre,Daniel Munro,Pejman Mohammadi,Lieselot L. G. Carrette,Olivier George,Abraham A. Palmer,Graham McVicker & Francesca Telese
Nature Neuroscience Published:05 October 2023
DOI:https://doi.org/10.1038/s41593-023-01452-y
Abstract
The amygdala processes positive and negative valence and contributes to addiction, but the cell-type-specific gene regulatory programs involved are unknown. We generated an atlas of single-nucleus gene expression and chromatin accessibility in the amygdala of outbred rats with high and low cocaine addiction-like behaviors following prolonged abstinence. Differentially expressed genes between the high and low groups were enriched for energy metabolism across cell types. Rats with high addiction index (AI) showed increased relapse-like behaviors and GABAergic transmission in the amygdala. Both phenotypes were reversed by pharmacological inhibition of the glyoxalase 1 enzyme, which metabolizes methylglyoxal—a GABAA receptor agonist produced by glycolysis. Differences in chromatin accessibility between high and low AI rats implicated pioneer transcription factors in the basic helix-loop-helix, FOX, SOX and activator protein 1 families. We observed opposite regulation of chromatin accessibility across many cell types. Most notably, excitatory neurons had greater accessibility in high AI rats and inhibitory neurons had greater accessibility in low AI rats.
