Syntaxin-1A () repression causes a neurodevelopmental disorder phenotype, low latent inhibition (LI) behavior, by disrupting 5-hydroxytryptaminergic (5-HTergic) systems. Herein, we discovered that lysine acetyltransferase (KAT) 3B increases neuronal transcription and TTK21, a KAT3 activator, induces transcription and 5-HT release . Furthermore, glucose-derived CSP-TTK21 could restore decreased expression, 5-HTergic systems in the brain, and low LI in (+/−) mice by crossing the blood-brain barrier, whereas the KAT3 inhibitor suppresses expression, 5-HTergic systems, and LI behaviors in wild-type mice. Finally, in wild-type and (−/−) mice treated with IKK inhibitors and CSP-TTK21, respectively, we show that KAT3 activator-induced LI improvement is a direct consequence of KAT3B- pathway, not a side effect. In conclusion, KAT3B can positively regulate transcription in neurons, and increasing neuronal expression and 5-HTergic systems by a KAT3 activator consequently improves the low LI behavior in the ablation mouse model.

中文翻译：

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KAT3 组蛋白乙酰转移酶家族激活剂可改善突触蛋白 1A 消融小鼠模型中的神经发育障碍表型

Syntaxin-1A () 抑制通过破坏 5-羟色胺能 (5-HTergic) 系统，导致神经发育障碍表型、低潜伏抑制 (LI) 行为。在此，我们发现赖氨酸乙酰转移酶 (KAT) 3B 会增加神经元转录，而 KAT3 激活剂 TTK21 会诱导转录和 5-HT 释放。此外，葡萄糖衍生的 CSP-TTK21 可以通过穿过血脑屏障来恢复大脑中 5-HTergic 系统的表达降低和 (+/-) 小鼠的低 LI，而 KAT3 抑制剂则抑制 5-HTergic 系统的表达，以及野生型小鼠的 LI 行为。最后，在分别用 IKK 抑制剂和 CSP-TTK21 治疗的野生型和 (−/−) 小鼠中，我们表明 KAT3 激活剂诱导的 LI 改善是 KAT3B 途径的直接结果，而不是副作用。总之，KAT3B 可以正向调节神经元中的转录，并且通过 KAT3 激活剂增加神经元表达和 5-HTergic 系统，从而改善消融小鼠模型中的低 LI 行为。