Publications by authors named "Emi Hasegawa"

Article Synopsis
  • DREADDs are advanced receptors that let scientists control neuron activity in living organisms, making it easier to study brain functions.
  • The newly developed miniD and miniD receptors are smaller versions of existing DREADDs, which help in both activating and inhibiting neuron activity.
  • Researchers successfully used a single viral vector to deliver these mini receptors, allowing them to manipulate brain activity effectively in monkeys, potentially enhancing research in brain regulation and behavior.
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The relationship between mental disorders and sleep remains unclear. Two new studies show that the lateral habenula, a brain region associated with value-guided behavior, controls REM sleep and promotes emotional stability but also contributes to REM sleep disinhibition in depression.

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  • The study investigates unknown drug interactions focusing on the role of drug-metabolizing CYP enzymes, specifically CYP3A4 and CYP1A2, using human HepaRG cells.* -
  • Rifampicin and omeprazole were found to induce CYP3A4 and CYP1A2 at the mRNA and protein levels, but omeprazole unexpectedly did not increase CYP3A4 protein despite inducing its mRNA.* -
  • The findings emphasize the need to expand drug-drug interaction assessments to consider post-translational regulation of CYP enzyme expression, in addition to traditional methods.*
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Article Synopsis
  • Temperature influences the core clock gene Per2, which is crucial for aligning the circadian clock with body temperature cycles.
  • Previous research indicated that the PI3K signaling pathway plays a role in Per2 protein expression during warm temperature shifts, but the complete signaling mechanisms are not fully understood.
  • This study identifies eIF2α kinases, specifically PKR and PERK, as new mediators of Per2 expression in response to temperature changes, functioning as upstream regulators of PI3K rather than via eIF2α.
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Animals have a sleep cycle that involves the repetitive occurrence of non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. In a previous study, we discovered that a transient increase in dopamine (DA) levels in the basolateral amygdala (BLA) during NREM sleep terminates NREM sleep and initiates REM sleep by acting on Drd2-positive neurons (Hasegawa et al., 2022).

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Skeletal muscle is programmable, and early-life nutritional stimuli may form epigenetic memory in the skeletal muscle, thus impacting adult muscle function, aging, and longevity. In the present study, we designed a one-month protein restriction model using post-weaning rats, followed by a two-month rebound feeding, to investigate how early-life protein restriction affects overall body growth and muscle development and whether these influences could be corrected by rebound feeding. We observed comprehensive alterations immediately after protein restriction, including retarded growth, altered biochemical indices, and disturbed hormone secretion.

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Background: Peritoneal dialysis (PD) is an important alternative treatment for end-stage renal disease. Continuous exposure to non-physiological fluids during PD is associated with pathological responses, such as sustained microinflammation, leading to tissue fibrosis and angiogenesis. However, the effect of PD fluid on submesothelial cells has not yet been investigated in detail.

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The sleep cycle alternates between REM and NREM sleep, but the mechanisms by which this cycle is generated are totally unknown. We found that a periodic transient increase of the dopamine level in the amygdala during NREM sleep terminates NREM sleep and initiates REM sleep. This mechanism also plays a role in cataplectic attack, which is a pathological intrusion of REM sleep into wakefulness in narcoleptics.

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The dorsal raphe nucleus (DRN) is known to control aggressive behavior in mice. Here, we found that glutamatergic projections from the lateral habenula (LHb) to the DRN were activated in male mice that experienced pre-exposure to a rival male mouse ("social instigation") resulting in heightened intermale aggression. Both chemogenetic and optogenetic suppression of the LHb-DRN projection blocked heightened aggression after social instigation in male mice.

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Structurally diverse small compounds are utilized to obtain hit compounds that have suitable pharmacophores in appropriate three-dimensional conformations for the target drug receptors. We have focused on the 1,3,5-trioxazatriquinane skeleton, which has a rigid bowl-like structure enabling the diverse orientation of side chain units, leading to a novel small-scale focused library based on the skeleton. In the library screening for the orexin receptor, some of the compounds showed orexin receptor antagonistic activity with a high hit rate of 7%.

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The sleep cycle is characterized by alternating non-rapid eye movement (NREM) and rapid eye movement (REM) sleeps. The mechanisms by which this cycle is generated are incompletely understood. We found that a transient increase of dopamine (DA) in the basolateral amygdala (BLA) during NREM sleep terminates NREM sleep and initiates REM sleep.

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A LC-MS/MS simultaneous analytical method for screening 191 pesticide residues in limes had been developed and validated. Pesticides were extracted with acetonitrile from samples. Then mixed salts, which were anhydrous magnesium sulfate for dehydration, sodium carbonate for adjusting pH, and sodium chloride for salting out, were added to the sample.

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The suprachiasmatic nucleus (SCN), the central circadian pacemaker in mammals, is a network structure composed of multiple types of γ-aminobutyric acid (GABA)-ergic neurons and glial cells. However, the roles of GABA-mediated signaling in the SCN network remain controversial. Here, we report noticeable impairment of the circadian rhythm in mice with a specific deletion of the vesicular GABA transporter in arginine vasopressin (AVP)-producing neurons.

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Hibernating mammals actively lower their body temperature to reduce energy expenditure when facing food scarcity. This ability to induce a hypometabolic state has evoked great interest owing to its potential medical benefits. Here we show that a hypothalamic neuronal circuit in rodents induces a long-lasting hypothermic and hypometabolic state similar to hibernation.

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We measured the residual amounts of chlorantraniliprole in various vegetables and fruits. Sample solutions were prepared according to our routine procedure based on the QuEChERS method and analyzed by LC-MS/MS. Performance characteristics were evaluated for 8 kinds of food samples by means of recovery tests of 5 replicates at the concentration of 10 ng/g.

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Article Synopsis
  • The study explores how sleep-wake behavior is regulated by specific neuron types in the ventral midbrain/pons (VMP) area of male mice.
  • Researchers found that killing GABAergic neurons in the VMP significantly increased wakefulness for up to 4 weeks, while killing dopaminergic neurons had minimal impact.
  • The findings highlight that GABAergic neurons play a crucial role in controlling sleep and wake patterns by interacting with the dopamine system, suggesting new mechanisms at play in sleep regulation.
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The hypothalamus plays an important role in the regulation of sleep/wakefulness states. While the ventrolateral preoptic nucleus (VLPO) plays a critical role in the initiation and maintenance of sleep, the lateral posterior part of the hypothalamus contains neuronal populations implicated in maintenance of arousal, including orexin-producing neurons (orexin neurons) in the lateral hypothalamic area (LHA) and histaminergic neurons in the tuberomammillary nucleus (TMN). During a search for neurons that make direct synaptic contact with histidine decarboxylase-positive (HDC+), histaminergic neurons (HDC neurons) in the TMN and orexin neurons in the LHA of male mice, we found that these arousal-related neurons are heavily innervated by GABAergic neurons in the preoptic area including the VLPO.

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Innate behaviors are genetically encoded, but their underlying molecular mechanisms remain largely unknown. Predator odor 2,4,5-trimethyl-3-thiazoline (TMT) and its potent analog 2-methyl-2-thiazoline (2MT) are believed to activate specific odorant receptors to elicit innate fear/defensive behaviors in naive mice. Here, we conduct a large-scale recessive genetics screen of ethylnitrosourea (ENU)-mutagenized mice.

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Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus (DRN) mediate the suppression of cataplexy-like episodes (CLEs) by orexin neurons. Using an optogenetic tool, in this paper we show that the acute activation of DRN serotonin neuron terminals in the amygdala, but not in nuclei involved in regulating rapid eye-movement sleep and atonia, suppressed CLEs.

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Although, the suprachiasmatic nucleus (SCN) of the hypothalamus acts as the central clock in mammals, the circadian expression of clock genes has been demonstrated not only in the SCN, but also in peripheral tissues and brain regions outside the SCN. However, the physiological roles of extra-SCN circadian clocks in the brain remain largely elusive. In response, we generated mice in which , an essential clock component, was genetically deleted specifically in the ventral forebrain, including the preoptic area, nucleus of the diagonal band, and most of the hypothalamus except the SCN.

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Article Synopsis
  • Continuous exposure to peritoneal dialysis fluids causes micro-inflammation and ultrafiltration failure, with Pentraxin-3 (PTX3) being a key response to inflammation.
  • A study using a rat model revealed that prolonged use of conventional dialysis fluid led to increased PTX3 levels and thickening of the peritoneal membrane.
  • High glucose in dialysis fluids was shown to significantly enhance PTX3 expression in various cell types, suggesting it plays a role in micro-inflammation associated with dialysis.
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The suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, is a network structure composed of multiple types of neurons. Here, we report that mice with a Bmal1 deletion specific to arginine vasopressin (AVP)-producing neurons showed marked lengthening in the free-running period and activity time of behavior rhythms. When exposed to an abrupt 8-hr advance of the light/dark cycle, these mice reentrained faster than control mice did.

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