Sleep Deprivation Induces Dopamine System Maladaptation and Escalated Corticotrophin-Releasing Factor Signaling in Adolescent Mice.

Sleep disruption is highly associated with the pathogenesis and progression of a wild range of psychiatric disorders. Furthermore, appreciable evidence shows that experimental sleep deprivation (SD) on humans and rodents evokes anomalies in the dopaminergic (DA) signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Since adolescence is a vital period for the maturation of the DA system as well as the occurrence of mental disorders, the present studies aimed to investigate the impacts of SD on the DA system of adolescent mice. We found that 72 h SD elicited a hyperdopaminergic status, with increased sensitivity to the novel environment and amphetamine (Amph) challenge. Also, altered neuronal activity and expression of striatal DA receptors were noticed in the SD mice. Moreover, 72 h SD influenced the immune status in the striatum, with reduced microglial phagocytic capacity, primed microglial activation, and neuroinflammation. The abnormal neuronal and microglial activity were putatively provoked by the enhanced corticotrophin-releasing factor (CRF) signaling and sensitivity during the SD period. Together, our findings demonstrated the consequences of SD in adolescents including aberrant neuroendocrine, DA system, and inflammatory status. Sleep insufficiency is a risk factor for the aberration and neuropathology of psychiatric disorders.

Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement.

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.