Astrocytes in the arcuate nucleus and median eminence that take up a fluorescent dye from the circulation express leptin receptors and neuropeptide Y Y1 receptors

Cheunsuang, Ornsiri; Morris, Richard

doi:10.1002/glia.20239

Cited by 77 publications

(59 citation statements)

References 36 publications

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“…There is a strong link between inflammation and cachexia, including both an association of inflammatory markers and cytokines with evidence of cachexia and evidence for a direct stimulation of central neurological centers, including the melanocortin system, by specific cytokines (14,15,53). Circulating cytokines can permeate the relatively weak blood-brain barrier at the level of the hypothalamus, or cytokines expressed centrally could activate the system (54). Indeed, many of the interventions attempted thus far to improve cachexia have targeted the associated inflammation (1).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Treatment of Chronic Kidney Disease: Improvements in Lean Body Mass and Cytokine Profile

et al. 2007

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Chronic kidney disease (CKD) is associated with an increase in inflammatory cytokines and can result in cachexia with loss of muscle and fat stores. We previously demonstrated the efficacy of treating a model of cancer cachexia with ghrelin and a ghrelin receptor agonist. Currently, we examine a surgical model of CKD in rats, resulting in uremia and decreased accrual of lean body mass. Treatment with ghrelin and two ghrelin receptor agonists (BIM-28125 and BIM-28131) resulted in increased food intake and an improvement in lean body mass accrual that was related in part to a decrease in muscle protein degradation as assessed by muscle levels of the 14-kDa actin fragment resulting from cleaved actomyosin. Additionally, there was a decrease in circulating inflammatory cytokines in nephrectomized animals treated with ghrelin relative to saline treatment. Ghrelin-treated animals also had a decrease in the expression of IL-1 receptor in the brainstem and a decrease in expression of prohormone convertase-2, an enzyme involved in the processing of proopiomelanocortin to the anorexigenic peptide ␣-MSH. We conclude that ghrelin treatment in uremia results in improved lean mass accrual in part due to suppressed muscle proteolysis and possibly related to antiinflammatory effects. (Endocrinology 149: 827-835, 2008) P ATIENTS WITH CHRONIC kidney disease (CKD) often exhibit symptoms of anorexia, loss of lean body mass, and increased energy expenditure, matching the syndrome of cachexia seen in other chronic diseases such as cancer, chronic heart failure, and AIDS (1, 2). In addition, patients with CKD-induced uremia frequently exhibit a dangerous decrease in protein nutritional status, including decreased levels of albumin and prealbumin as well as catabolism of actinomycin in muscle tissue via caspase-3 and the ubiquitinproteasome pathway (3-8). As with other diseases associated with cachexia, these catabolic processes seen in CKD are linked to systemic inflammatory changes, including increases in acute-phase reactants such as C-reactive protein and inflammatory cytokines (9 -15). Indeed, this inflammation is felt to be in the causative pathway of the production of cachexia (16 -19).CKD is similar to other diseases associated with cachexia in that the symptoms of cachexia in CKD are associated with a decrease in quality of life and an increase in mortality (20 -26). Unfortunately, no single agent has emerged as a beneficial treatment for cachexia (27). One potential treatment for cachexia in multiple disease states is the use of the orexigenic hormone ghrelin (28, 29). Although ghrelin levels are already elevated above normal in cachexia-associated disease states such as cancer, heart failure, and CKD, administration of supraphysiological doses of ghrelin has been shown to increase food intake in human subjects with cancer and heart failure (30 -34).We have previously delivered ghrelin and ghrelin agonists in a rat model of cancer cachexia, demonstrating improved lean body mass retention and increases in gene expression of ag...

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Section: Discussionmentioning

confidence: 99%

Ghrelin Treatment of Chronic Kidney Disease: Improvements in Lean Body Mass and Cytokine Profile

et al. 2007

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“…The activities of astrocytes in the Arc and ME may be also be regulated by other signaling pathways of peripheral small-molecules, such as thymulin. After all, without the blood-brain barrier, circulating molecules were taken up by astrocytes in Arc and ME (Cheunsuang & Morris 2005, Morita & Miyata 2013. Thus, it is unclear whether the effect and regulation of thymulin on GnRH is direct or mediated by astrocytes.…”

Section: Figurementioning

confidence: 99%

Effects of GnRH immunization on the reproductive axis and thymulin

Su¹,

Sun²,

Zhou³

et al. 2015

Journal of Endocrinology

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The bidirectional regulation of thymulin in the reproductive-endocrine function of the hypothalamic-pituitary-gonadal (HPG) axis of rats immunized against GnRH remains largely unclear. We explored the alterations in hormones in the HPG axis in immunized rats to dissect the repressive effect of immunization on thymulin, and to clarify the interrelation of reproductive hormones and thymulin in vivo. The results showed that, in the first 2 weeks of booster immunization, thymulin was repressed when reproductive hormones were severely reduced. The self-feedback regulation of thymulin was then stimulated in later immune stages: the rising circulating thymulin upregulated LH and FSH, including GnRH in the hypothalamus, although the levels of those hormones were still significantly lower than in the control groups. In astrocytes, thymulin produced a feedback effect in regulated GnRH neurons. However, in the arcuate nucleus (Arc) and the median eminence (ME), the mediator of astrocytes and other glial cells were also directly affected by reproductive hormones. Thus, in immunized rats, the expression of glial fibrillary acidic protein was distinctly stimulated in the Arc and ME. This study demonstrated that thymulin was downregulated by immunization against GnRH in early stage. Subsequently, the self-feedback regulation was provoked by low circulating thymulin. Thereafter, rising thymulin levels promoted pituitary gonadotropins levels, while acting directly on GnRH neurons, which was mediated by astrocytes in a region-dependent manner in the hypothalamus.

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“…Astrocytes express LEPR (Cheunsuang & Morris 2005, Hsuchou et al 2009b, and modifications in circulating leptin levels alter hypothalamic astrocyte expression of structural proteins as well as glutamate and glucose transporters , Fuente-Martin et al 2012. This may cause changes in the synaptic plasticity and excitability of surrounding neurons, leading to metabolic adaptations.…”

Section: New Players In Energy Balance Controlmentioning

confidence: 99%

Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance

Schneeberger¹,

Gomis²,

Claret³

2014

Journal of Endocrinology

234

199

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Alterations in adequate energy balance maintenance result in serious metabolic disturbances such as obesity. In mammals, this complex process is orchestrated by multiple and distributed neuronal circuits. Hypothalamic and brainstem neuronal circuits are critically involved in the sensing of circulating and local factors conveying information about the energy status of the organism. The integration of these signals culminates in the generation of specific and coordinated physiological responses aimed at regulating energy balance through the modulation of appetite and energy expenditure. In this article, we review current knowledge on the homeostatic regulation of energy balance, emphasizing recent advances in mouse genetics, electrophysiology, and optogenetic techniques that have greatly contributed to improving our understanding of this central process.

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Astrocytes in the arcuate nucleus and median eminence that take up a fluorescent dye from the circulation express leptin receptors and neuropeptide Y Y1 receptors

Cited by 77 publications

References 36 publications

Ghrelin Treatment of Chronic Kidney Disease: Improvements in Lean Body Mass and Cytokine Profile

Ghrelin Treatment of Chronic Kidney Disease: Improvements in Lean Body Mass and Cytokine Profile

Effects of GnRH immunization on the reproductive axis and thymulin

Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance

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