Search

This article, published in the journal Cell Discovery, explores the role of leptin receptor neurons in the ventral premammillary nucleus (PMv) in modulating emotion-induced insomnia. The study found that exposure to emotional stimuli, such as urine or TMT (a component of fox odor), significantly delayed non-rapid eye movement (NREM) sleep onset and increased wakefulness in mice. The researchers also discovered that PMvLepR neurons were activated by emotional stimuli and that their activation led to prolonged wakefulness, mimicking insomnia-like behavior. Inhibition of PMvLepR neurons abolished the increase in sleep latency and wakefulness following emotional stimuli. These findings suggest that PMvLepR neurons may be an important therapeutic target for managing emotion-induced insomnia. [Extracted from the article]

Summary: Insomnia is one of the most prevalent sleep disorders, which imparts tremendous societal and economic impact. However, the present pharmacotherapy is greatly limited by adverse effects, so it is necessary to explore new drugs for the treatment of insomnia. Radix Bupleuri (RB) has been widely used in traditional Chinese medicine for >2000 years; it has many pharmacological effects, including sedation and anticonvulsant properties. The present study investigated the effects of saikosaponin a (SSa), an active component of RB, on sleep and locomotion. Male C57BL/6j mice received intraperitoneal injections of SSa at three different dosages (0.625, 1.25, and 2.5 mg/kg). Sleep parameters were analysed by electroencephalography and electromyography. The open‐field test was used to measure locomotor activities. Our present results showed that SSa treatment significantly increased the duration of non‐rapid eye movement sleep and shortened sleep latency in a dose‐dependent manner. A high dose of SSa (2.5 mg/kg) also decreased locomotor activities. Moreover, by measuring c‐Fos expression and the calcium signal in the lateral hypothalamus (LH), we found that SSa treatment decreased neuronal activity in the LH. In conclusion, SSa might be the sleep‐promoting component in RB and its mechanism may be related to the modulation of neuronal activity in the LH. [ABSTRACT FROM AUTHOR]

The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved in sleep–wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on, which persisted until after lesions of 25 days. Similarly, pharmacological and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep. Electrophysiological experiments combined with optogenetics showed a direct inhibitory connection between the terminals of RMTg neurons and midbrain dopaminergic neurons. The bidirectional effects of the RMTg on the sleep–wake cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic approach. Furthermore, during the 2-hour recovery period following 6-hour sleep deprivation, the amount of NREM sleep in both the lesion and control rats was significantly increased compared with baseline levels; however, only the control rats showed a significant increase in SWA compared with baseline levels. Collectively, our findings reveal an essential role of the RMTg in the promotion of NREM sleep and homeostatic regulation. [ABSTRACT FROM AUTHOR]

Glutamate is the major excitatory neurotransmitter in the brain and plays an essential role in regulating wakefulness. Histaminergic neurons, which are exclusively localized in the tuberomammillary nucleus (TMN) of the hypothalamus, have a pivotal role in the regulation of sleep–wake patterns by sending widespread projections into many brain areas implicated in sleep–wake control. The role of glutamate in histaminergic neurons within the TMN and the resulting sleep–wake profile remains unknown. We found that glutamate, NMDA, AMPA or dihydrokainate, a glutamate-uptake inhibitor, dose-dependently increased wakefulness when microinjected into the rat TMN. Glutamate, NMDA, and AMPA also increased the firing rate of action potentials in TMN histaminergic neurons. The arousal-promoting effect of glutamate was inhibited by NMDA and histamine H 1 receptor antagonists. Furthermore, MK-801, an NMDA receptor antagonist, inhibited the firing rate of histaminergic neurons and increased non-rapid eye movement sleep after microinjection into rat TMN. Taken together, these findings demonstrated that glutamate activated histaminergic neurons in the TMN and increased wakefulness in rats, possibly via the action of NMDA and histamine H 1 receptors. • Glutamate and its receptor agonist NMDA and AMPA increase wakefulness in rats. • Glutamate, NMDA and AMPA activate the histaminergic neurons in TMN. • The effect of glutamate was inhibited by NMDAR and histamine H 1 R antagonists. [ABSTRACT FROM AUTHOR]

Interleukin-1β (IL-1β) and prostaglandin (PG) D 2 are endogenous sleep-promoting substances. Since it was reported that a highly selective cyclooxygenase-2 (COX-2) inhibitor, NS398, completely inhibited IL-1β-induced sleep in rats, IL-1β-induced sleep had been believed to be mediated by prostanoids, most probably PGD 2 . However, in the present study, pretreatment of rats with NS398 (3 mg/kg) did not suppress the 64.2% increased non-rapid eye movement (non-REM, NREM) sleep during infusion of IL-1β (10 ng) for 6 h in the nocturnal (active) period between 23:00 and 5:00 into the subarachnoid space of the PGD 2 -sensitive sleep-promoting zone of the basal forebrain. Meanwhile, IL-1β at doses of 1.7 and 5 μg/kg also significantly increased NREM sleep for 6 h after intraperitoneal injection at 20:00 (light-off time) by 76.8% and 121.1%, respectively, in wild-type (WT) mice, by 67.7% and 147.3%, respectively, in WT mice pretreated with NS398 (5 mg/kg) and by 108.9% and 121.6%, respectively, in PGD 2 receptor (DP 1 R) knockout mice. These results indicate that IL-1β-induced NREM sleep is independent of the PGD 2 /DP 1 R system and other COX-2-derived prostaglandins in rats and mice. [ABSTRACT FROM AUTHOR]

The olfactory tubercle (OT), an important nucleus in processing sensory information, has been reported to change cortical activity under odor. However, little is known about the physiological role and mechanism of the OT in sleep-wake regulation. The OT expresses abundant adenosine A 2A receptors (A 2A Rs), which are important in sleep regulation. Therefore, we hypothesized that the OT regulates sleep via A 2A Rs. This study examined sleep-wake profiles through electroencephalography and electromyography recordings with pharmacological and chemogenetic manipulations in freely moving rodents. Compared with their controls, activation of OT A 2A Rs pharmacologically and OT A 2A R neurons via chemogenetics increased non-rapid eye movement sleep for 5 and 3 h, respectively, while blockade of A 2A Rs decreased non-rapid eye movement sleep. Tracing and electrophysiological studies showed OT A 2A R neurons projected to the ventral pallidum and lateral hypothalamus, forming inhibitory innervations. Together, these findings indicate that A 2A Rs in the OT play an important role in sleep regulation. • Activation of OT A 2A Rs increased NREM sleep. • Blockade of OT A 2A Rs increased sleep latency. • Chemogenetic activation of OT A 2A R neurons increased NREM sleep. • Connections between OT A 2A R neurons and neurons in the VP and LH were inhibitory. • The study concluded that the OT promotes sleep through A 2A Rs and A2AR neurons. [ABSTRACT FROM AUTHOR]