Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement
Journal
PLoS biology
Journal Volume
17
Journal Issue
3
Date Issued
2019-03
Author(s)
Teng, Ling-Ling
Lu, Guan-Ling
Lin, Wei-Sheng
Cheng, Ya-Yun
Hsueh, Tai-En
Huang, Yi-Ching
Hwang, Nai-Hsuan
Yeh, Jin-Wei
Liao, Ruey-Ming
Yen, Jui-Hung
Fu, Tsai-Feng
Tsai, Ting-Fen
Abstract
Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake.
SDGs
Type
journal article