Induction of Fos protein in neurons in the medulla oblongata after motion- and X-irradiation-induced emesis in musk shrews (Suncus murinus)

Ito, Hisao; Nishibayashi, Mitsuru; Kawabata, Keita; Maeda, Seishi; Seki, Makoto; Ebukuro, Susumu

doi:10.1016/s1566-0702(03)00026-2

Cited by 27 publications

(39 citation statements)

References 15 publications

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“…The minor differences are likely due to the different emetogens used. The discussed studies also indicate that while some emetic stimuli induce Fos expression in the AP, others don't [31,36]. In the current study, GR73632 had no significant effect on Fos-IR in the AP.…”

Section: Central and Peripheral Mechanisms Contribute To Emetic Behaviorcontrasting

confidence: 42%

“…Although the effect of an NK 1 receptor agonist on emesis-related Fos induction in the DVC of an emetic species has not yet been reported, other emetic stimuli induce strong Fos expression in neurons in the medial subnucleus of the NTS, and less robustly but significantly in the DMNX, of vomiting species including the house musk shrew [4,31,36,45,57]. Analysis of Fos-IR demonstrated that systemic administration of an emetic dose of GR73632 produced a similar expression pattern in the medial subnucleus of the NTS and in the DMNX of the least shrew.…”

Section: Central and Peripheral Mechanisms Contribute To Emetic Behaviormentioning

confidence: 98%

“…The NTS is impacted by numerous emesis-mediating afferents (e.g. vagal afferents) and serves as a major integrating site for diverse emetic stimuli [2,5,31,57], but does not directly generate motor activity. Thus, increased Fos-IR in the NTS is more likely to be related to induction of emesis rather than the motoric expression of vomiting.…”

Section: Central and Peripheral Mechanisms Contribute To Emetic Behaviormentioning

confidence: 99%

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Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists

et al. 2008

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Substance P (SP) is thought to play a cardinal role in emesis via the activation of central tachykinin NK 1 receptors during the delayed phase of vomiting produced by chemotherapeutics. Although the existing supportive evidence is significant, due to lack of an appropriate animal model, the evidence is indirect. As yet, no study has confirmed that emesis produced by SP or a selective NK 1 receptor agonist is sensitive to brain penetrating antagonists of either NK 1 , NK 2 , or NK 3 receptors. The goals of this investigation were to demonstrate: 1) whether intraperitoneal (i.p.) administration of either SP, a brain penetrating (GR73632) or non-penetrating (e.g. SarMet -SP) NK 1 receptor agonist, an NK 2 receptor agonist (GR64349), or an NK 3 receptor agonist (Pro 7 -NKB), would induce vomiting and/or scratching in the least shrew (Cryptotis parva) in a dose-dependent manner; and whether these effects are sensitive to the above selective receptor antagonists; 2) whether an exogenous emetic dose of SP (50 mg/kg, i.p.) can penetrate into the shrew brain stem and frontal cortex; 3) whether GR73632 (2.5 mg/kg, i.p.)-induced activation of NK 1 receptors increases Fos-measured neuronal activity in the neurons of both brain stem emetic nuclei and the enteric nervous system of the gut; and 4) whether selective ablation of peripheral NK 1 receptors can affect emesis produced by GR73632. The results clearly demonstrated that while SP produced vomiting only, GR73632 caused both emesis and scratching behavior dose-dependently in shrews, and these effects were sensitive to NK 1 -, but not NK 2 -or NK 3 -receptor antagonists. Neither the selective, non-penetrating NK 1 receptor agonists, nor the selective NK 2 -or NK 3 -receptor agonists, caused a significant dose-dependent behavioral effect. An emetic dose of SP selectively and rapidly penetrated the brain stem but not the frontal cortex. Systemic GR73632 increased Fos expression in the enteric nerve plexi, the medial subnucleus of nucleus tractus solitarius, and the dorsal motor nucleus of the vagus, but not the area postrema. Ablation of peripheral NK 1 receptors attenuated the ability of GR73632 to induce a maximal frequency of emesis and shifted its percent animals vomiting dose-response curve to the right. The NK 1 -ablated shrews exhibited scratching behavior after systemic GR73632-injection. These results, for the first time, affirm a cardinal role for central NK 1 receptors in SP-induced vomiting, and a Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. facilitatory role for gastrointestinal NK 1 receptors. In addition, the...

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Section: Central and Peripheral Mechanisms Contribute To Emetic Behaviorcontrasting

confidence: 42%

Section: Central and Peripheral Mechanisms Contribute To Emetic Behaviormentioning

confidence: 98%

Section: Central and Peripheral Mechanisms Contribute To Emetic Behaviormentioning

confidence: 99%

See 1 more Smart Citation

Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists

et al. 2008

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“…Brainstem SP has been implicated in autonomic control [16,29] and in control of emetic reflexes [41,46,48]. Of greatest relevance to the current use of C. parva as a small-animal emesis model, SP was found in the brainstem areas held to be key mediators of the emetic reflex: The area postrema, solitary tract and nucleus, and dorsal motor nucleus of the vagus nerve [4,[24][25][26]31]. Interestingly, preliminary results using c-fos immunohistochemistry as a marker for neuronal activation suggest that following the delayedphase emetic response, fos is increased most strongly in areas associated with dense SPL-IR fiber plexi (Ray, unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

“…While rodent pica behavior has been used as a substitute for vomiting [24], it is unclear whether the neural substrates of this behavior are truly the same or similar enough for use as an emetic model. For a more appropriate model of emesis, researchers have turned to the insectivorous Soricid shrews, the house musk shrew [Suncus murinus; [25]] and the least shrew [Cryptotis parva; [11]], and to the carnivorous ferret [Mustela sp. ; [51]] and cat [Felis domesticus; [32]].…”

Section: Introductionmentioning

confidence: 99%

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

Ray

Darmani

2007

Brain Research

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Chemotherapy is an effective treatment but difficult to tolerate due to side effects like vomiting. Studies on the etiology of chemotherapy-related emesis have implicated brainstem nuclei and the neurotransmitter Substance P, among other substrates. Since rodents do not vomit, other species have been necessary as alternative models of chemotherapy-induced emesis. Of these, the least shrew (Cryptotis parva) has proven valuable due to its small size, hardiness, and close phylogenetic relationship with primates. However, very little neuroanatomical data on C. parva exist. We used histological and immunohistochemical techniques to provide neuroanatomical data to help validate C. parva as a model organism, especially for emesis research. Brains were sectioned and stained for Nissl substance or myelin, or immunofluorescently labeled for Substance P. Sections were photographed, traced, and reconstructed with standardized zero points, and these data used to create a stereotaxic atlas. The brain of C. parva was similar to but smaller than other mammalian brains, with the cerebellum and hippocampus demonstrating the biggest differences. Differences appeared to be related to the small size of the brain and the metabolic compromises required of such a small mammal. Substance P-like immunoreactivity (SPL-IR) was semiquantitatively mapped, and correlated very well with SPL-IR observed in other species. Dense SPL-IR areas included the periaqueductal grey, trigeminal nuclei, dorsal raphe, and emesis-related brainstem nuclei including the area postrema and solitary tract nucleus. These data demonstrate that the anatomical differences between C. parva and other mammals will not preclude its use as a model organism.

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Generation and characterization of Suncus murinus intestinal organoid: a useful tool for studying motilin secretion

Takakura

Takemi

Kumaki

et al. 2019

Cell Biology International

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Motilin, a 22‐amino‐acid peptide produced in the upper small intestine, induces strong gastric contraction in fasted state. In many rodents, motilin and its cognate receptors exist as pseudogenes, which has delayed motilin research in the past decades. Recently, the house musk shrew (Suncus murinus) was developed as a useful model for studying motilin and gastrointestinal motility. However, due to a lack of motilin‐producing cell lines and difficulties in culturing small intestinal cells, the regulatory mechanisms of motilin secretion and its messenger RNA (mRNA) transcription have remained largely unclear. In this study, we generated small intestinal organoids from S. murinus for the first time. Using methods similar to mouse organoid generation, we found crypt‐like budding structures 3 days after isolating intestinal tissues. The organoids grew gradually with time. In addition, the generated organoids were able to be passaged and maintained for 6 months or longer. Motilin messenger RNA (mRNA) and immunopositive cells were observed in both S. murinus intestinal organoids and primary tissues. This is the first report of intestinal organoids in S. murinus, and our results suggest that S. murinus intestinal organoids could be useful for analyzing motilin secretion and transcription.

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Induction of Fos protein in neurons in the medulla oblongata after motion- and X-irradiation-induced emesis in musk shrews (Suncus murinus)

Cited by 27 publications

References 15 publications

Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists

Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

Generation and characterization of Suncus murinus intestinal organoid: a useful tool for studying motilin secretion

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