Takahiro Nakayama, Akash K Singh, Toshiyuki Fukutomi, Noriyuki Uchida, Yasuo Terao, Hiroki Hamada, Takahiro Muraoka, Eswaramoorthy Muthusamy, Tapas K Kundu, Kimio Akagawa
Syntaxin-1A (stx1a) 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 stx1a neuronal transcription and TTK21, a KAT3 activator, induces stx1a transcription and 5-HT release in vitro. Furthermore, glucose-derived CSP-TTK21 could restore decreased stx1a expression, 5-HTergic systems in the brain, and low LI in stx1a (+/-) mice by crossing the blood-brain barrier, whereas the KAT3 inhibitor suppresses stx1a expression, 5-HTergic systems, and LI behaviors in wild-type mice...
April 11, 2024: Cell Reports