Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Department of Neurogenetics, Pavlov Institute of Physiology, 199034 Saint Petersburg, Russia.
Biomolecules. 2022 May 26;12(6):751. doi: 10.3390/biom12060751.
The gasotransmitter hydrogen sulfide (HS) produced by the transsulfuration pathway (TSP) is an important biological mediator, involved in many physiological and pathological processes in multiple higher organisms, including humans. Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) enzymes play a central role in HS production and metabolism. Here, we investigated the role of HS in learning and memory processes by exploring several strains with single and double deletions of CBS and CSE developed by the CRISPR/Cas9 technique. We monitored the learning and memory parameters of these strains using the mating rejection courtship paradigm and demonstrated that the deletion of the gene, which is expressed predominantly in the central nervous system, and double deletions completely block short- and long-term memory formation in fruit flies. On the other hand, the flies with deletion preserve short- and long-term memory but fail to exhibit long-term memory retention. Transcriptome profiling of the heads of the males from the strains with deletions in terms revealed a strong down-regulation of many genes involved in learning and memory, reproductive behavior, cognition, and the oxidation-reduction process in all strains with deletion, indicating an important role of the hydrogen sulfide production in these vital processes.
硫化氢（HS）作为转硫途径（TSP）产生的一种气体递质，是一种重要的生物介质，参与包括人类在内的多种高等生物的许多生理和病理过程。胱硫醚-β-合酶（CBS）和胱硫醚-γ-裂解酶（CSE）酶在 HS 的产生和代谢中起着核心作用。在这里，我们通过探索由 CRISPR/Cas9 技术开发的具有 CBS 和 CSE 单和双缺失的几种菌株，研究了 HS 在学习和记忆过程中的作用。我们使用交配拒绝求偶范式监测这些菌株的学习和记忆参数，并证明在果蝇中，主要在中枢神经系统中表达的 基因缺失和双缺失完全阻断了短期和长期记忆的形成。另一方面，具有 缺失的苍蝇保留了短期和长期记忆，但不能表现出长期记忆保留。缺失 基因的雄性蝇头的转录组分析揭示，所有缺失 基因的菌株中，许多参与学习和记忆、生殖行为、认知以及氧化还原过程的基因都被强烈下调，表明 HS 的产生在这些重要过程中起着重要作用。
