Nesfatin-1 in the dorsal raphe nucleus influences visceral sensitivity via 5-HT neurons in male maternally separated rats

Zhang, Hui-Ai; Sang, Nan; Xian, Ge; Huang, Qian; Li, Xueliang; Sha, Jie

doi:10.1038/s41598-018-27592-x

Cited by 8 publications

(4 citation statements)

References 36 publications

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“…In addition, sensitization and upregulation of microglial toll-like receptor 4 (TLR4) signaling activity in the PVN (Tang et al, 2017), ephrin-B2/EphB1 spinal signaling pathway (Theofanous et al, 2020), and nerve growth factor (NGF)-mediated tropomyosin receptor kinase A (TrkA) signaling (Wong et al, 2019) were involved in MS-induced visceral hypersensitivity. Moreover, various important signaling molecule dysfunctions were also involved in MS-induced visceral hypersensitivity, such as elevated expression of Nesfatin-1 in the dorsal raphe nucleus (DRN) (Zhang et al, 2018). Together, these studies focused the mechanism of MS-induced visceral hypersensitivity in adulthood.…”

Section: Discussionmentioning

confidence: 99%

Maternal Separation Induced Visceral Hypersensitivity Evaluated via Novel and Small Size Distention Balloon in Post-weaning Mice

et al. 2022

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Early life stress (ELS) disposes to functional gastrointestinal diseases in adult, such as irritable bowel syndrome (IBS). Maternal separation (MS) is a well-known animal model of IBS and has been shown to induce visceral hypersensitivity in adult rats and mice. However, to the best of our knowledge, it has not been reported whether MS induces visceral hypersensitivity in young mice, such as the post-weaning mice. Moreover, the method for evaluation of visceral sensitivity also has not been described. Accordingly, the present study aims to evaluate the visceral sensitivity caused by MS in post-weaning mice and develop a novel and small size distention balloon for assessment of visceral sensitivity of such mice. Male pups of C57BL/6 mice were randomly divided into two groups, MS (n = 12) and non-separation (NS) (n = 10). MS pups were separated from the dams through postnatal days (PND) 2 to 14, while NS pups were undisturbed. After, all pups stayed with respective dams and were weaned at PND 22. Visceral sensitivity was evaluated by colorectal distention (CRD) with a novel and small size distention balloon at PND 25. The threshold of abdominal withdrawal reflex (AWR) scores were significantly lower in MS than NS. In addition, AWR scores at different pressures of CRD were significantly higher in MS than NS. The results demonstrate that MS induced visceral hypersensitivity in post-weaning mice. The designed small size distention balloon for evaluation of visceral sensitivity is of significance to further study the pathophysiology of IBS from early life to adulthood.

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Section: Discussionmentioning

confidence: 99%

Maternal Separation Induced Visceral Hypersensitivity Evaluated via Novel and Small Size Distention Balloon in Post-weaning Mice

et al. 2022

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“…This system can send fibers in a top-down manner to the dorsal spinal horn to inhibit pain transmission (Millan, 2002). The system comprises of the PAG, DR, rostral-ventromedial medulla (RVM), and LC (Reynolds, 1969;Francois et al, 2017;Torralba et al, 2018;Zhang et al, 2018). The system also sends dense connections to the CSF-contacting nucleus, which might be a novel pathway in pain modulation.…”

Section: Painmentioning

confidence: 99%

Connection Input Mapping and 3D Reconstruction of the Brainstem and Spinal Cord Projections to the CSF-Contacting Nucleus

Song

Zhai

et al. 2020

Front. Neural Circuits

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Objective: To investigate whether the CSF-contacting nucleus receives brainstem and spinal cord projections and to understand the functional significance of these connections. Methods: The retrograde tracer cholera toxin B subunit (CB) was injected into the CSF-contacting nucleus in Sprague-Dawley rats according the previously reported stereotaxic coordinates. After 7-10 days, these rats were perfused and their brainstem and spinal cord were sliced (thickness, 40 µm) using a freezing microtome. All the sections were subjected to CB immunofluorescence staining. The distribution of CBpositive neuron in different brainstem and spinal cord areas was observed under fluorescence microscope. Results: The retrograde labeled CB-positive neurons were found in the midbrain, pons, medulla oblongata, and spinal cord. Four functional areas including one hundred and twelve sub-regions have projections to the CSF-contacting nucleus. However, the density of CB-positive neuron distribution ranged from sparse to dense. Conclusion: Based on the connectivity patterns of the CSF-contacting nucleus receives anatomical inputs from the brainstem and spinal cord, we preliminarily conclude and summarize that the CSF-contacting nucleus participates in pain, visceral activity, sleep and arousal, emotion, and drug addiction. The present study firstly illustrates the broad projections of the CSF-contacting nucleus from the brainstem and spinal cord, which implies the complicated functions of the nucleus especially for the unique roles of coordination in neural and body fluids regulation.

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“…Some studies have suggested that central and peripheral nervous factors are involved in this process. For example, the activation of DRN 5-HT neurons might play a crucial role in visceral hypersensitivity [13], and impaired 5-HT reuptake by intestinal epithelial cells could lead to elevated levels of 5-HT in the colon, which could potentially influence the pathogenesis of IBS-D [14]. Therefore, how to restore the 5-HT equilibrium in the DRN (central) and intestine (peripheral) poses a challenge in the treatment of IBS-D.…”

Section: Introductionmentioning

confidence: 99%

Regulation of the MCHergic Neural Circuit to Dorsal Raphe Nucleus on Emotion-Related Behaviors and Intestinal Dysfunction in Mice Model of Irritable Bowel Syndrome with Diarrhea

Ming,

Gao,

Sun

et al. 2024

Neuroendocrinology

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Introduction: Irritable bowel syndrome with diarrhea (IBS-D) is frequently accompanied by depression and anxiety, resulting in a reduced quality of life and increased medical expenditures. Although psychological factors are known to play an important role in the genesis and development of IBS-D, an understanding of the central neural control of intestinal dysfunction remains elusive. Melanin-concentrating hormone (MCH) is a gut-brain peptide involved in regulating feeding, sleep-wake rhythms, and emotional states. Methods: This study investigated the regulation of the MCHergic neural circuit from the lateral hypothalamic area (LHA) to the dorsal raphe nucleus (DRN) on anxiety- and depression-like behaviors, intestinal motility, and visceral hypersensitivity in a mice model of IBS-D. The models of IBS-D were prepared by inducing chronic unpredictable mild stress. Results: Chemogenetic activation of the MCH neurons in the LHA could excite serotonin (5-HT) neurons in the DRN and induce anxiety- and depression-like behaviors and IBS-D-like symptoms, which could be recovered by microinjection of the MCH receptor antagonist SNAP94847 into the DRN. The mice model of IBS-D showed a reduction of 5-HT and brain-derived neurotrophic factor (BDNF) expression in the DRN, while an elevation of 5-HT and BDNF was observed in the colon through immunofluorescent staining, ELISA, and Western blot analysis. SNAP94847 treatment in the DRN alleviated anxiety- and depression-like behaviors, improved intestinal motility, and alleviated visceral hypersensitivity responses by normalizing the 5-HT and BDNF expression in the DRN and colon. Conclusion: This study suggests that the activation of MCH neurons in the LHA may induce IBS-D symptoms via the DRN and that the MCH receptor antagonist could potentially have therapeutic effects.

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Nesfatin-1 in the dorsal raphe nucleus influences visceral sensitivity via 5-HT neurons in male maternally separated rats

Cited by 8 publications

References 36 publications

Maternal Separation Induced Visceral Hypersensitivity Evaluated via Novel and Small Size Distention Balloon in Post-weaning Mice

Maternal Separation Induced Visceral Hypersensitivity Evaluated via Novel and Small Size Distention Balloon in Post-weaning Mice

Connection Input Mapping and 3D Reconstruction of the Brainstem and Spinal Cord Projections to the CSF-Contacting Nucleus

Regulation of the MCHergic Neural Circuit to Dorsal Raphe Nucleus on Emotion-Related Behaviors and Intestinal Dysfunction in Mice Model of Irritable Bowel Syndrome with Diarrhea

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