Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice

He, Xiaoman; Li, Yuhang; Zhang, Nana; Huang, Jinfang; Ming, Xing; Guo, Ruixiao; Hu, Yang; Ji, Pengfei; Guo, Feifei

doi:10.3389/fphar.2022.906057

Cited by 12 publications

(10 citation statements)

References 84 publications

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“…3 G–I ). The absence of differences in our study in center/border preference in the open field—a measure of anxiety-like behavior—upon experimental manipulations of the MCH system may seem in contrast with past studies reporting that blockade of the MCHR1 receptor exerts an anxiolytic effect ( Borowsky et al, 2002 ; Roy et al, 2006 ; He et al, 2022 ). However, other studies on the role of the MCH system in anxiety-related behaviors have yielded contrasting results ( Kela et al, 2003 ; Basso et al, 2006 ).…”

Section: Discussioncontrasting

confidence: 99%

Exploratory Rearing Is Governed by Hypothalamic Melanin-Concentrating Hormone Neurons According to Locus Ceruleus

Concetti,

Viskaitis,

Grujic

et al. 2024

J. Neurosci.

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Information seeking, such as standing on tiptoes to look around in humans, is observed across animals and helps survival. Its rodent analog – unsupported rearing on hind legs – was a classic model in deciphering neural signals of cognition, and is of intense renewed interest in preclinical modeling of neuropsychiatric states. Neural signals and circuits controlling this dedicated decision to seek information remain largely unknown. While studying sub-second timing of spontaneous behavioral acts and activity of MCH neurons (MNs) in behaving male and female mice, we observed large MN activity spikes that aligned to unsupported rears. Complementary causal, loss and gain of function, analyses revealed specific control of rear frequency and duration by MNs and MCHR1 receptors. Activity in a key stress center of the brain – thelocus coeruleusnoradrenaline cells – rapidly inhibited MNs, and required functional MCH receptors for its endogenous modulation of rearing. By defining a neural module that both tracks and controls rearing, these findings may facilitate further insights into biology of information seeking.Significance StatementAnimals, including humans, use movement to interact with their environment - to reach specific targets or gain information, as when standing tall and looking around. Information-seeking is a fundamental behavior related to cognition and neuropsychiatric states. However, the neural circuits underlying it are still unclear. We show that hypothalamic neurons make melanin-concentrating hormone (“MN”) are active during a well-known rodent analog of information-seeking – rearing on hind limbs - and contribute to driving these acts of rearing. We also find thatlocus coeruleusnoradrenergic neurons, known for mediating stress responses, inhibit MNs, thus providing a neural link between stress and information-seeking. These results identify a neural substrate of information-seeking, and provide insights into how the brain toggles between conflicting, survival-critical priorities.

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Section: Discussioncontrasting

confidence: 99%

Exploratory Rearing Is Governed by Hypothalamic Melanin-Concentrating Hormone Neurons According to Locus Ceruleus

Concetti,

Viskaitis,

Grujic

et al. 2024

J. Neurosci.

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“…Although MCH infusion did not increase food seeking in an anxiogenic context, the orexigenic effects of MCH may have been masked by MCH-mediated anxiogenesis (Smith et al, 2006;He et al, 2022). We thus determined if MCH infusion in the LS increased anxiety-like behaviour in sex and MCH (F(1, 12) = 0.523; p = 0.480).…”

Section: Ls Mch Infusion Did Not Alter Anxiety-like Behaviourmentioning

confidence: 96%

Melanin-concentrating hormone promotes feeding through the lateral septum

Payant,

Shankhatheertha,

Chee

2024

Preprint

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Feeding is necessary for survival but can be hindered by anxiety or fear, thus neural systems that can regulate anxiety states are key to elucidating the expression of food-related behaviors. Melanin-concentrating hormone (MCH) is a neuropeptide produced in the lateral hypothalamus that promotes feeding and anxiogenesis. The orexigenic actions of MCH that prolong ongoing homeostatic or hedonic feeding are context-dependent and more prominent in male than female rodents, but it is not clear where MCH acts to initiate feeding. The lateral septum (LS) promotes feeding and suppresses anxiogenesis when inhibited, and it comprises the densest projections from MCH neurons. However, it is not known whether the LS is a major contributor to MCH-mediated feeding. As MCH inhibits LS cells by MCH receptor (MCHR1) activation, MCH may promote feeding via the LS. We bilaterally infused MCH into the LS and found that MCH elicited a rapid and long-lasting increase in the consumption of standard chow and a palatable, high sugar diet in male and female mice; these MCH effects were blocked by the co-administration of a MCHR1 antagonist TC- MCH 7c. Interestingly, the orexigenic effect of MCH was abolished in a novel, anxiogenic environment even when presented with a food reward, but MCH did not induce anxiety-like behaviors. These findings indicated the LS as a novel region underlying orexigenic MCH actions, which stimulated and enhanced feeding in both sexes in a context -dependent manner that was most prominent in the homecage.

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“…20 In fact, the stress or corticosterone injection can activate MCH neurons, and blocking the MCH receptor has anti-anxiety effects. 6,21 It has been established that MCH stimulates the HPA axis predominantly through the corticotrophin-releasing hormone neurons of the paraventricular nucleus 7 ; thus, this study attempted to investigate the impact of chrysin on MCH mRNA levels. The ICV injection of chrysin significantly downregulated hypothalamic MCH gene expression in stressed rats.…”

Section: Stress Is An Endocrine Disorder That Leads To Healthmentioning

confidence: 99%

The Influences of Chrysin on Stress-Induced Changes of Melanin-Concentrating Hormone and Orexin Gene Expression in Rats

Haghighat,

Mahmoudi,

Khazali

2024

Int J Basic Sci Med

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Introduction: Chrysin is a bioactive component of herbal medicines such as Passiflora incarnate, Passiflora caerulea, and Oroxylum indicum. Although evidence has demonstrated the neuroprotective, anti-inflammatory, and pain-relieving effects of chrysin, the intra-hypothalamic molecular mechanisms underlying the anxiolytic effects of chrysin are still unclear. This study aimed to explore the effects of chrysin on hypothalamic orexin and melanin-concentrating hormone (MCH) gene expression in a rat model of stress. Methods: Twenty male Wistar rats (200±10 g) were segregated into four groups (n=5). For the induction of stress, the animals were placed in the restraint cage for 2 hours. The intact and stressed groups received saline. Thirty minutes before the induction of stress, chrysin was injected into the other two groups of the stress model at a dosage of 20 or 40 µg via the third cerebral ventricle. Hypothalamic samples were removed and frozen, and the relative gene expression of orexin and MCH was measured using the real-time polymerase chain reaction technique. Results: The induction of stress significantly increased mRNA levels of orexin and MCH compared to the control rats. The mRNA levels of MCH and orexin significantly declined in rats receiving chrysin compared to the stress group. Conclusion: The inhibition of the hypothalamic MCH and orexin neuronal circuits may be involved in the preventive effects of chrysin against stressful situations. Chrysin may be a potential target to manage anxiogenic behaviors due to the down-regulation of MCH and orexin gene expression upstream the hypothalamic corticotropin-releasing hormone.

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Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice

Cited by 12 publications

References 84 publications

Exploratory Rearing Is Governed by Hypothalamic Melanin-Concentrating Hormone Neurons According to Locus Ceruleus

Exploratory Rearing Is Governed by Hypothalamic Melanin-Concentrating Hormone Neurons According to Locus Ceruleus

Melanin-concentrating hormone promotes feeding through the lateral septum

The Influences of Chrysin on Stress-Induced Changes of Melanin-Concentrating Hormone and Orexin Gene Expression in Rats

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