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Women are more vulnerable to stress and have a higher likelihood of developing mood disorders. The serotonin (5HT) system has been highly implicated in stress response and mood regulation. However, sex-dependent mechanisms underlying serotonergic regulation of stress vulnerability remain poorly understood. Here, we report that adult hippocampal neural stem cells (NSCs) of the Ascl1 lineage (Ascl1-NSCs) in female mice express functional 5HT1A receptors (5HT1ARs), and selective deletion of 5HT1ARs in Ascl1-NSCs decreases the Ascl1-NSC pool only in females. Mechanistically, 5HT1AR deletion in Ascl1-NSCs of females leads to 5HT-induced depolarization mediated by upregulation of 5HT7Rs. Furthermore, repeated restraint stress (RRS) impairs Ascl1-NSC maintenance through a 5HT1AR-mediated mechanism. By contrast, Ascl1-NSCs in males express 5HT7R receptors (5HT7Rs) that are downregulated by RRS, thus maintaining the Ascl1-NSC pool. These findings suggest that sex-specific expression of distinct 5HTRs and their differential interactions with stress may underlie sex differences in stress vulnerability. [Display omitted] • Adult mouse Ascl1-NSCs express 5HT1ARs in females, while they express 5HT7Rs in males • 5HT1AR deletion in Ascl1-NSCs of females impairs NSCs via upregulation of 5HT7Rs • Stress upregulates 5HT7Rs in Ascl1-NSCs of females and reduces NSCs via 5HT1ARs • Stress downregulates 5HT7Rs in Ascl1-NSCs of males, and NSCs are maintained Luo et al. report sex-specific expression of distinct 5HTRs in adult mouse neural stem cells (NSCs) and their differential interaction with stress in regulating NSCs. Specifically, stress upregulates 5HT7Rs in NSCs of females and reduces the NSC pool via 5HT1ARs, while it downregulates 5HT7Rs in NSCs of males and maintains the NSC pool. [ABSTRACT FROM AUTHOR]

Adult hippocampal neurogenesis (AHN) plays a key role in modulating memory and emotion processing. A fundamental question remains on how to effectively modulate AHN to improve hippocampal function. Here, we review recent work on how distinct aspects of hippocampal neurogenesis, including the number, maturation state, and activity of adult-born neurons (ABNs), contribute to overall hippocampal function. We propose multi-level enhancement of hippocampal neurogenesis with the combination of increased number, elevated activity, and enhanced maturation of ABNs as a potential strategy to optimize overall hippocampal performance. In addition, integration of ABNs induces significant remodeling of the local hippocampal circuits, which may in turn modulates brain-wide network dynamics. We discuss recent progress on how integration of ABNs contributes to local hippocampal circuit and brain-wide network dynamics during behavior. • The number, maturation state, and activity of adult-born neurons contribute to distinct aspects of hippocampal function. • Multi-level enhancement of hippocampal neurogenesis optimizes overall hippocampal performance. • Integration of adult-born neurons modulates local hippocampal circuit and brain-wide network dynamics. [ABSTRACT FROM AUTHOR]

Abstract: Magnolol (6,6′,7,12-tetramethoxy-2,2′-dimethyl-1-beta-berbaman, C18H18O2), an active ingredient of the bark of Magnolia officinalis, has been reported to exert potent anti-epileptic effects via the GABAA receptor. The receptor also mediates sleep in humans and animals. The aim of this study was to determine whether magnolol could modulate sleep behaviors by recording EEG and electromyogram in mice. The results showed that magnolol administered i.p. at a dose of 5 or 25 mg/kg could significantly shorten the sleep latency, increase the amount of non-rapid eye movement (non-REM, NREM) and rapid eye movement (REM) sleep for 3 h after administration with an increase in the number of NREM and REM sleep episodes. Magnolol at doses of 5 and 25 mg/kg increased the number of bouts of wakefulness but decreased their duration. On the other hand, magnolol increased the number of state transitions from wakefulness to NREM sleep and subsequently from NREM sleep to wakefulness. Immunohistochemical study showed that magnolol increased c-Fos expression in the neurons of ventrolateral preoptic area, a sleep center in the anterior hypothalamus, and decreased c-Fos expression in the arousal tuberomammillary nucleus, which was located in the caudolateral hypothalamus. The sleep-promoting effects and changes in c-Fos induced by magnolol were reversed by flumazenil, an antagonist at the benzodiazepine site of the GABAA receptor. These results indicate that magnolol increased NREM and REM sleep via the GABAA receptor. [Copyright &y& Elsevier]