Publication in Neuroscience

Pr. Urade, Dr Aritake and their collaborators published their results in Journal of Sleep Research.

Interleukin-1β induces sleep independent of prostaglandin D2 in rats and mice



Interleukin-1β (IL-1β) and prostaglandin (PG) D2 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 PGD2. However, in the present study, pretreatment of rats with NS398 (3mg/kg) did not suppress the 64.2% increased non-rapid eye movement (non-REM, NREM) sleep during infusion of IL-1β (10ng) for 6h in the nocturnal (active) period between 23:00 and 5:00 into the subarachnoid space of the PGD2-sensitive sleep-promoting zone of the basal forebrain. Meanwhile, IL-1β at doses of 1.7 and 5μg/kg also significantly increased NREM sleep for 6h 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 (5mg/kg) and by 57.9% and 121.6%, respectively, in PGD2 receptor (DP1R) knockout mice. These results indicate that IL-1β-induced NREM sleep is independent of the PGD2/DP1R system and other COX-2-derived prostaglandins in rats and mice.

Publication in Advances in Neurobiology

Pr. Urade, Dr Aritake and their collaborators published their results in Journal of Sleep Research.

Neuroprotective Activities of Saffron and Crocin



We first considered that saffron is really safety food because it has a long-use history. The neuroprotective activities of saffron and its major constituent, crocin, are separately discussed in vitro and in vivo. We reviewed the inhibitory activities of crocin against PC-12 cell apoptosis. The oxidative stress decreased the cellular levels of glutathione (GSH) which is an inhibitor of neutral sphingomyelinase (N-SMase). Therefore, the level of GSH was assayed by the addition of crocin resulted in the activation of glutathione reductase (GR). It became evident that crocin treatment prevents the N-SMase activation resulting in the decrease of ceramide release. From these evidences we summarized the role of crocin for neuronal cell death. We used the ethanol-blocking assay system for learning and memory activities. The effect of saffron and crocin on improving ethanol-induced impairment of learning behaviors of mice in passive avoidance tasks has been clear. Further, we did make clear that saffron and crocin prevent the inhibitory effect of ethanol on long-term potentiation (LTP) in the dentate gyrus. Finally we found that 100 mg/kg of crocin gave non-rapid eye movement sleep (non-REM sleep) although mice were started to be active during night time.

JSPS Kakenhi grants’ results 2016 – part 2

Urade Laboratory’s great work has been (again) rewarded this year!

Dr. Malyshevskaya got rewarded by a grant Research Activity Start-Up for the next 2 years. Congratulations!


JSPS Kakenhi


Publication in Brain Structure & function

Dr.Cherasse and his collaborators published their results in Brain Structure & Function.

Adenosine A2A receptors in the olfactory bulb suppress rapid eye movement sleep in rodents.



Rapid eye movement (REM) sleep behavior disorder in humans is often accompanied by a reduced ability to smell and detect odors, and olfactory bulbectomized rats exhibit increased REM sleep, suggesting that the olfactory bulb (OB) is involved in REM-sleep regulation. However, the molecular mechanism of REM-sleep regulation by the OB is unknown. Adenosine promotes sleep and its A2A receptors (A2AR) are expressed in the OB. We hypothesized that A2AR in the OB regulate REM sleep. Bilateral microinjections of the A2AR antagonist SCH58261 into the rat OB increased REM sleep, whereas microinjections of the A2AR agonist CGS21680 decreased REM sleep. Similar to the A2AR antagonist, selective A2AR knockdown by adeno-associated virus carrying short-hairpin RNA for A2AR in the rat OB increased REM sleep. Using chemogenetics on the basis of designer receptors exclusively activated by designer drugs, we demonstrated that the inhibition of A2AR neurons increased REM sleep, whereas the activation of these neurons decreased REM sleep. Moreover, using a conditional anterograde axonal tract-tracing approach, we found that OB A2AR neurons innervate the piriform cortex and olfactory tubercle. These novel findings indicate that adenosine suppresses REM sleep via A2AR in the OB of rodents.


Publication in Journal of Sleep Research

Yoshitaka Nakamura, a PhD student in our group, recently published his results in Journal of Sleep Research. Congratulations!

Oral administration of Japanese sake yeast (Saccharomyces cerevisiae sake) promotes non-rapid eye movement sleep in mice via adenosine A2A receptors



We have demonstrated previously that Japanese sake yeast improves sleep quality in humans. In the present study, we examined the molecular mechanisms of sake yeast to induce sleep by monitoring locomotor activity, electromyogram and electroencephalogram in mice. Oral administration of Japanese sake yeast (100, 200, and 300 mg kg−1) decreased the locomotor activity by 18, 46 and 59% and increased the amount of non-rapid eye movement (NREM) sleep by 1.5-, 2.3- and 2.4-fold (to 37 ± 6, 57 ± 8, and 60 ± 4 min from 25 ± 6 min in the vehicle-administered group, respectively) in a dose-dependent manner for 4 h after oral administration. However, Japanese sake yeast did not change the amount of rapid eye movement (REM) sleep, the electroencephalogram power density during NREM sleep or show any adverse effects, such as rebound of insomnia, during 24 h postadministration and on the next day. An intraperitoneal pretreatment with an adenosine A2A receptor-selective antagonist, ZM241385 (15 mg kg−1), reduced the amount of NREM sleep of sake yeast-administered mice to the basal level, without changing basal amount of sleep. Conversely, an A1 receptor-selective antagonist, 8-cyclopentyltheophylline (10 mg kg−1), did not affect the sleep-promoting effect of Japanese sake yeast. Thus, Japanese sake yeast promotes NREM sleep via activation of adenosine A2A but not A1 receptors.


JSPS Kakenhi grants’ results 2016

Urade Laboratory’s great work has been rewarded this year!

Pr. Urade got rewarded by a grant in Aid for Scientists A (Kiban A) for the next 3 years.

Dr. Cherasse received a 3 years Grant-in-aid for Young Scientists B (Kakenhi Wakate B).

Good luck to you all with your research projects, may you be successful and the force be with you.

JSPS Kakenhi


Publication in eNeuro

Dr. Kaushik and his collaborators published their results in eNeuro.

Specific Targeting of the Basolateral Amygdala to Projectionally Defined Pyramidal Neurons in Prelimbic and Infralimbic Cortex.



Adjacent prelimbic (PL) and infralimbic (IL) regions in the medial prefrontal cortex have distinct roles in emotional learning. A complete mechanistic understanding underlying this dichotomy remains unclear. Here we explored targeting of specific PL and IL neurons by the basolateral amygdala (BLA), a limbic structure pivotal in pain and fear processing. In mice, we used retrograde labeling, brain-slice recordings, and adenoviral optogenetics to dissect connectivity of ascending BLA input onto PL and IL neurons projecting to the periaqueductal gray (PAG) or the amygdala. We found differential targeting of BLA projections to PL and IL cortex. Activating BLA projections evoked excitatory and inhibitory responses in cortico-PAG (CP) neurons in layer 5 (L5) of both PL and IL cortex. However, all inhibitory responses were polysynaptic and monosynaptic BLA input was stronger to CP neurons in IL cortex. Conversely, the BLA preferentially targeted corticoamygdalar (CA) neurons in layer 2 (L2) of PL over IL cortex. We also reveal that BLA input is projection specific by showing preferential targeting of L5 CP neurons over neighboring L3/5 CA neurons in IL cortex. We conclude by showing that BLA input is laminar-specific by producing stronger excitatory responses CA neurons in L3/5 compared with L2 in IL cortex. Collectively, this study reveals differential targeting of the BLA to PL and IL cortex, which depends both on laminar location and projection target of cortical neurons. Overall, our findings should have important implications for understanding the processing of pain and fear input by the PL and IL cortex.


Final report NARO 2016

The sleep consortium presented its conclusions at the NARO final report, in Tokyo Akihabara.

The poster presentation was a great success with many people interested to know how zinc supplementation can become beneficial for health!

20160318_134842  20160318_160232


New comer

Urade Laboratory is happy to welcome a new comer.

Ms Ito is joining our group as a replacement of Ms Hasegawa.

Welcome and good luck in your new journey into sleep science.


Publication in Journal of Visualized Experiments

Pr. Urade and his collaborators published their results in Journal of Visualized Experiments.

Polygraphic Recording Procedure for Measuring Sleep in Mice.



Recording of the epidural electroencephalogram (EEG) and electromyogram (EMG) in small animals, like mice and rats, has been pivotal to study the homeodynamics and circuitry of sleep-wake regulation. In many laboratories, a cable-based sleep recording system is used to monitor the EEG and EMG in freely behaving mice in combination with computer software for automatic scoring of the vigilance states on the basis of power spectrum analysis of EEG data. A description of this system is detailed herein. Steel screws are implanted over the frontal cortical area and the parietal area of 1 hemisphere for monitoring EEG signals. In addition, EMG activity is monitored by the bilateral placement of wires in both neck muscles. Non-rapid eye movement (Non-REM; NREM) sleep is characterized by large, slow brain waves with delta activity below 4 Hz in the EEG, whereas a shift from low-frequency delta activity to a rapid low-voltage EEG in the theta range between 6 and 10 Hz can be observed at the transition from NREM to REM sleep. By contrast, wakefulness is identified by low- to moderate-voltage brain waves in the EEG trace and significant EMG activity.