Activation of Calcium‐Sensing Receptor in the Area Postrema Inhibits Food Intake via Glutamatergic and GABAergic Signaling Pathways

Huang, Jinfang; Qian, Xu; Li, Yuhang; He, Xiaoman; Guo, Yajie; Sun, Xiangrong

doi:10.1002/mnfr.202200245

Cited by 4 publications

(3 citation statements)

References 43 publications

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“…The AP/NTS/PBN circuit has previously been described to be critical for learning food avoidance and Zhang and colleagues demonstrated that cinacalcet administration activated GLP1R-positive neurons in the AP to reinforce a flavor avoidance response 21 . Additionally, Huang et al showed that injection of NPS R568 (an early calcimimetic) directly into the AP activated glutaminergic neurons that acutely inhibited food intake 65 . We confirmed those observations by showing first, that the CaSR is expressed in the AP (and not in the NTS or PBN) and that the approximately 13% of AP cells that express the CaSR also express the GLP1R.…”

Section: Discussionmentioning

confidence: 99%

Cancer-Associated Hypercalcemia Signals Through the Hindbrain to cause Anorexia

Grinman,

Takyar,

Dann

et al. 2024

Preprint

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Hypercalcemia, caused by tumor secretion of parathyroid hormone-related protein (PTHrP), is associated with anorexia and weight loss. We demonstrate that overexpression of PTHrP by tumor cells in a transgenic model of breast cancer causes anorexia and rapid weight loss. These changes are accompanied by activation of neurons in the area postrema (AP), the nucleus tractus solitarius (NTS) and the parabrachial nucleus (PBN), a hindbrain circuit regulating food intake. Blocking hypercalcemia prevents anorexia and activation of these brain centers in tumor bearing mice, whereas injecting calcium activates the same circuit in wild-type mice. Neurons in the AP express the calcium-sensing receptor (CaSR) and the same AP/NTS/PBN circuit is stimulated by treating WT mice with cinacalcet, an allosteric activator of the CaSR. Finally, treating diet-induced obese mice with cinacalcet reduces food intake and causes weight loss. These results suggest that CaSR-expressing neurons in the AP might be a pharmacologic target for obesity.

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Section: Discussionmentioning

confidence: 99%

Cancer-Associated Hypercalcemia Signals Through the Hindbrain to cause Anorexia

Grinman,

Takyar,

Dann

et al. 2024

Preprint

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“…One important thing to be addressed here is that the area postrema (AP), another critical CVO in the brain that also expresses AT 1 R 64,65 and is implicated in food intake control, [66][67][68] is a possible target where ANG II might influence food intake. While the AP does not exhibit the same relevance as the SFO in water intake regulation, its connectivity with the hypothalamus and its role in regulating food intake 67 makes it a potential target of interest for future investigations. Furthermore, it is essential to note that this study was conducted exclusively in male rats, despite the known impact of biological sex on the RAS 69,70 and neuroendocrine control of hydromineral balance.…”

Section: Discussionmentioning

confidence: 99%

Fasting increases circulating angiotensin levels and brain Agtr1a expression in male rats

Paes‐Leme

Monteiro

Gholami

et al. 2023

J Neuroendocrinology

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Besides being recognised for involvement in cardiovascular control and hydromineral balance, the renin‐angiotensin system (RAS) has also been associated with the neuroendocrine control of energy balance. One of the main brain sites for angiotensin II (ANG II)/type 1 receptor (AT1R) signalling is the subfornical organ (SFO), a circumventricular organ related to the control of autonomic functions, motivated behaviours and energy metabolism. Thus, we hypothesised that circulating ANG II may act on the SFO AT1R receptors to integrate metabolic and hydromineral balance. We evaluated whether food deprivation can modulate systemic RAS activity and Agrt1a brain expression, and if ANG II/AT1R signalling influences the hypothalamic expression of mRNAs encoding neuropeptides and food and water ingestion in fed and fasted Wistar rats. We found a significant increase in both ANG I and ANG II plasma levels after 24 and 48 hours of fasting. Expression of Agrt1a mRNA in the SFO and paraventricular nucleus (PVN) also increased after food deprivation for 48 h. Treatment of fasted rats with low doses of losartan in drinking water attenuated the decrease in glycemia and meal‐associated water intake without changing the expression in PVN or arcuate nucleus of mRNAs encoding selected neuropeptides related to energy homeostasis control. These findings point to a possible role of peripheral ANG II/SFO‐AT1R signalling in the control of re‐feeding‐induced thirst. On the other hand, i.c.v. losartan treatment decreased food and water intake over dark time in fed but not in fasted rats.This article is protected by copyright. All rights reserved.

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“…The sections were rinsed three times with PBS for 5 min each, followed by mounting with antifadent solutions. All sections were visualized and photographed using a BX50 microscope and DP50 digital camera [33]. Immunoreactive cells were tallied in five regions across five brain slices from both the LHA and DRN of each mouse.…”

Section: Methodsmentioning

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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Activation of Calcium‐Sensing Receptor in the Area Postrema Inhibits Food Intake via Glutamatergic and GABAergic Signaling Pathways

Cited by 4 publications

References 43 publications

Cancer-Associated Hypercalcemia Signals Through the Hindbrain to cause Anorexia

Cancer-Associated Hypercalcemia Signals Through the Hindbrain to cause Anorexia

Fasting increases circulating angiotensin levels and brain Agtr1a expression in male rats

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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