Publications by authors named "Yasutake Shimizu"

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  • Hibernating animals can significantly lower their body temperature without damaging their organs, potentially due to active hypometabolism.
  • Researchers studied the phosphorylation of Akt to see if metabolism decreases during artificial hypothermia in hamsters.
  • They found that while hypothermia through adenosine A1 receptor activation decreased Akt phosphorylation significantly, anesthesia-induced hypothermia showed only partial reduction without organ damage, indicating both methods allow for regulated metabolic reduction.
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  • The study examined how a ghrelin agonist, RQ-00538053, affects colorectal motility in female versus male rats, finding that it boosted motility in females but required much higher doses than in males.
  • Even when delivered directly to the lumbosacral spinal cord, female rats still needed tenfold higher doses for similar effects, indicating a significant sex difference in response.
  • Analysis revealed lower levels of ghrelin receptor expression in female rats' spinal cords, suggesting this might explain the varying effectiveness of the agonist, which is key for future research on treating constipation with ghrelin agonists.
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  • Purines like ATP play a crucial role in regulating the movement of the gastrointestinal tract, particularly in esophageal motility.
  • Researchers conducted an experiment using isolated rat esophagus segments, finding that ATP induces relaxation of esophageal smooth muscle after precontraction.
  • The relaxation mechanism involves the activation of P2Y receptors and the opening of ATP-dependent potassium channels, while certain receptor antagonists can inhibit this effect.
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The tunica muscularis of mammalian esophagi is composed of striated muscle and smooth muscle. Contraction of the esophageal striated muscle portion is mainly controlled by cholinergic neurons. On the other hand, smooth muscle contraction and relaxation are controlled not only by cholinergic components but also by non-cholinergic components in the esophagus.

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  • Patients with Parkinson's disease often experience constipation, which is believed to be due to issues in the central nervous system regulating colorectal motility.
  • A study on PD model rats showed that while capsaicin typically stimulates colorectal activity, it failed to do so in PD rats unless certain conditions, like blocking GABA receptors, were met.
  • The results indicate that in Parkinson's disease, there's a shift from serotonin's stimulatory effect to GABA's inhibitory effect in the pathways controlling bowel movements, providing insight into constipation issues faced by PD patients.
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Distinct sex differences in the prevalence and symptoms of abnormal bowel habits in patients with irritable bowel syndrome (IBS) have been reported. We have elucidated the sex differences in the regulation of colorectal motility via the central nervous system. Noxious stimuli in the colorectum of anesthetized male rats enhance colorectal motility by activating monoaminergic neurons in descending pain inhibitory pathways from the brainstem to the lumbosacral spinal cord.

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The supraspinal brain regions controlling defecation reflex remain to be elucidated. The purpose of this study was to determine the roles of the hypothalamic A11 region and the medullary raphe nuclei in regulation of defecation. For chemogenetic manipulation of specific neurons, we used the double virus vector infection method in rats.

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Noxious stimuli on the colorectum cause colorectal contractions through activation of descending monoaminergic pathways projecting from the supraspinal defecation center to the spinal defecation center. Since it is known that substance P is involved in the response to peripheral noxious stimuli in the spinal cord, we investigated the effects of intrathecally administered substance P at L6-S1 levels on colorectal motility in rats that were anesthetized with α-chloralose and ketamine. Intrathecally administered substance P enhanced colorectal motility, even after transection of the thoracic spinal cord at the T4 level.

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Our recent studies have shown that noxious stimuli in the colorectum enhance colorectal motility via the brain and spinal defecation centers in male rats. In female rats, however, noxious stimuli have no effect on colorectal motility. The purpose of this study was to determine whether sex hormones are major contributing factors for sex-dependent differences in neural components of the spinal defecation center.

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  • Torpor is a reduced metabolic state that could have medical benefits.
  • Researchers found that house musk shrews enter torpor when ambient temperature drops below 20°C without needing to fast or have reduced light.
  • The study suggests that these shrews could serve as a useful model for studying torpor mechanisms, which could lead to methods for inducing artificial hibernation in other species, including humans.
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  • The study developed a new way to induce deep hypothermia in rats using isoflurane anesthesia, finding that cooling led to cardiac arrest if inhalation continued past a certain temperature.
  • Stopping isoflurane inhalation at a rectal temperature of 22.5 °C allowed for the successful induction of deep hypothermia, while stopping at 27.5 °C led to recovery without achieving the desired cooling.
  • The method maintained hypothermic conditions for up to 6 hours with some organ injury observed, which was temporary and resolved within a week, suggesting the procedure is safe for inducing deep hypothermia in rats.
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The central nervous system is involved in regulation of defaecation. It is generally considered that supraspinal regions control the spinal defaecation centre. However, signal transmission from supraspinal regions to the spinal defaecation centre is still unclear.

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  • The study found that male and female rats respond differently to painful stimuli in the colorectum, with males showing increased colorectal motility when exposed to capsaicin, while females did not.
  • Researchers discovered that serotonin and dopamine neurons are primarily involved in male responses, enhancing motility, whereas females' responses are influenced by GABAergic neurons, which may inhibit this activation.
  • This research sheds light on the biological mechanisms behind sex differences in certain gastrointestinal disorders, like irritable bowel syndrome.
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G protein-coupled receptor (GPR) 37 and GPR37L1 are known to modulate the dopaminergic neuron activity, and recently, they are identified as candidate prosaposin receptors. Intercellular prosaposin is proteolytically processed into four saposins, each of which acts as a sphingolipid hydrolase activator in the lysosome. In contrast, extracellular prosaposin exerts a trophic effect on neurons via GPR37 and GPR37L1.

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Multiple mRNA isoforms are often generated during processing such as alternative splicing of precursor mRNAs (pre-mRNA), resulting in a diversity of generated proteins. Alternative splicing is an essential mechanism for the functional complexity of eukaryotes. Temperature, which is involved in all life activities at various levels, is one of regulatory factors for controlling patterns of alternative splicing.

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  • Researchers explored the roles of the locus coeruleus (LC) and A11 dopaminergic region in stimulating colorectal contractions and found that activating these brainstem nuclei enhanced defecation reflexes.
  • Stimulation of the LC and A11 increased colorectal pressure but only when a blocker for GABA receptors was used in the spinal cord.
  • The study concluded that these brain regions act as control centers for defecation, relying on specific receptors to facilitate their effects on colorectal motility.
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  • CIRBP is a protein that helps protect organisms from cold temperatures and has various splicing variants found in different animals, including hamsters and mice.
  • In mice, several splicing variants of CIRBP mRNA were identified, and a specific short form variant became more prominent during induced hypothermia.
  • The study suggests that low temperatures significantly influence the alternative splicing of CIRBP, indicating that this regulatory mechanism exists in both hibernating and non-hibernating species.
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  • The study focused on the role of ATP-dependent potassium channels (K channels) in controlling the movement of striated muscle in the esophagus.
  • In experiments, blocking K channels with glibenclamide led to stronger muscle contractions, while activating them with minoxidil weakened contractions.
  • The presence of K channel subunits was confirmed in esophageal tissue, suggesting they play a significant part in regulating muscle activity in this area.
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  • Cold-shock proteins play a key role in the cold tolerance of hibernating animals, with a focus on an RNA-binding protein (CIRBP) that is rapidly induced in hamsters' hearts through alternative splicing.
  • While CIRBP mRNA is consistently expressed across various organs in nonhibernating hamsters, hibernating hamsters predominantly show a short variant of CIRBP necessary for function.
  • Maintaining hamsters in mild hypothermia for an adequate duration triggers a shift in alternative splicing, which mimics the gradual temperature decrease seen during natural hibernation.
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  • The study investigates how peristalsis in the esophagus is regulated, focusing on the striated muscle area, using an innovative method in anesthetized rats.
  • The researchers used a balloon-tipped catheter to induce peristalsis by inflating the balloon, establishing a relationship between the volume and speed of inflation and the effectiveness of inducing peristaltic motility.
  • Key findings reveal the importance of both inflation velocity and nitric oxide in initiating peristalsis, suggesting that factors like mucosal afferent fibers may modulate mechanosensor activity necessary for this process.
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  • Some rodents, like squirrels and hamsters, hibernate, causing significant changes in body temperature and energy expenditure to adapt to cold environments.
  • During hibernation, the heart continues to beat while adjustments occur in calcium management within cardiac cells to prevent overload and maintain functional calcium levels.
  • The expression of the cold-inducible RNA-binding protein (CIRP) in the hearts of hibernating hamsters is regulated through alternative splicing, allowing for a quick response to the demands of hibernation.
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  • The spinal defecation center's role in regulating defecation is not fully understood, but the study reveals that monoamines like norepinephrine, dopamine, and serotonin can induce contractions in the colorectum when injected.
  • Capsaicin, a noxious stimulus, was shown to trigger transient propulsive contractions in the colorectal region, and this effect could be inhibited by blocking specific neurotransmitter receptors in the spinal defecation center.
  • The findings suggest that harmful stimuli activate pathways that enhance colorectal motility, contributing to our understanding of how the body responds to discomfort in this area.
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  • The presence of a fecal pellet in the colorectum triggers coordinated contractions and relaxations to efficiently push the pellet out of the body.
  • Research using balloons to monitor rectal motility in anesthetized rats revealed that the presence of a balloon enhances motility toward the anus while inhibiting motions toward the mouth, indicating a local reflex mechanism.
  • Disruption of the enteric nervous system impaired this local reflex, suggesting that an intrinsic regulatory mechanism exists to optimize bowel movements, and its dysfunction may contribute to issues like post-inflammation dysmotility in the colorectum.
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  • Colorectal motility is influenced by two brain and spinal cord defecation centers, with serotonin (5-HT) playing a crucial role in enhancing movement.
  • Stimulation of the medullary raphe nuclei initially did not improve motility; however, blocking GABA receptors allowed the stimulation to increase colorectal contractions.
  • Activation of the raphe nuclei enhances motility through pelvic nerves and 5-HT receptors in the lumbosacral spinal cord, highlighting the complex interaction between different neurotransmitters in regulating bowel function.
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Neuronal nuclear antigen (NeuN), discovered in mice brain cell nuclei by Mullen et al. (1992), is used as an excellent marker of post-mitotic neurons in vertebrates. In this study, the expression pattern of NeuN was examined in the Xenopus brain to explore phylogenetic differences in NeuN expression.

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