Transgenic Mice Expressing Green Fluorescent Protein under the Control of the Corticotropin-Releasing Hormone Promoter

Alon, Tamar; Zhou, Ligang; Pérez, Cristián A.; Garfield, Alastair S.; Friedman, Jeffrey M.; Heisler, Lora K.

doi:10.1210/en.2009-0881

Cited by 62 publications

(73 citation statements)

References 24 publications

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“…The GPe receives most of its afferent fibers from the striatal indirect pathway coexpressing GABA (Kita and Kitai, 1988) and enkephalin (Haber and Watson, 1983;Gerfen and Young, 1988). In animals that have been pretreated with intracerebroventricular injections of colchicine, we could not find cell bodies with CRF immunoreactivity in the striatum (data not shown), in accordance with previous studies (Keegan et al, 1994;Alon et al, 2009). However, some nerve processes with CRF immunoreactivity could be detected projecting from the central amygdala to the most ventral part of the GPe.…”

Section: Discussionsupporting

confidence: 92%

An Anxiolytic Role for CRF Receptor Type 1 in the Globus Pallidus

Sztainberg¹,

Kuperman²,

Justice³

et al. 2011

J. Neurosci.

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Corticotropin-releasing factor receptor type 1 (CRFR1) plays a major role in the regulation of neuroendocrine and behavioral responses to stress and is considered a key mediator of anxiety behavior. The globus pallidus external (GPe), a main relay center within the basal ganglia that is primarily associated with motor and associative functions, is one of the brain nuclei with the highest levels of CRFR1 expression in the rodent brain. However, the role of CRFR1 in the GPe is yet unknown. In the present study, we used a lentiviral-based system of RNA interference to show that knockdown of CRFR1 mRNA expression in the GPe of adult mice induces a significant increase in anxiety-like behavior, as revealed by the light-dark transfer, open-field, and elevated plus-maze tests. This effect was further confirmed by pharmacological administration of the selective CRFR1 antagonist NBI 30775 (1.75 g/side) directly into the GPe. In the marble-burying test, blockade of CRFR1 in the GPe increased the percentage of marbles buried and the duration of burying behavior. Additionally, we present evidence suggesting that the enkephalin system is involved in the effect of GPe-CRFR1 on anxiety-like behavior. In contrast to the well established anxiogenic role of CRFR1 in the extended amygdala, our data reveal a novel anxiolytic role for CRFR1 in the GPe.

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Section: Discussionsupporting

confidence: 92%

An Anxiolytic Role for CRF Receptor Type 1 in the Globus Pallidus

Sztainberg¹,

Kuperman²,

Justice³

et al. 2011

J. Neurosci.

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“…The CRH neurons are activated by both fasting and feeding and thus are uniquely positioned to affect lipolysis and adipogenesis (30,31). Paraventricular nucleus (PVN) CRH neurons innervate WAT directly (32,33).…”

Section: Discussionmentioning

confidence: 99%

Melanocortin-3 receptor regulates the normal fasting response

Renquist

Murphy

Larson

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The melanocortin-3 receptor-deficient (MC3-R −/− ) mouse exhibits mild obesity without hyperphagia or hypometabolism. MC3-R deletion is reported to increase adiposity, reduce lean mass and white adipose tissue inflammation, and increase sensitivity to salt-induced hypertension. We show here that the MC3-R −/− mouse exhibits defective fasting-induced white adipose tissue lipolysis, fasting-induced liver triglyceride accumulation, fasting-induced refeeding, and fasting-induced regulation of the adipostatic and hypothalamic-adrenal-pituitary axes. Close examination of the hypothalamic-pituitary-adrenal axis showed that MC3-R −/− mice exhibit elevated nadir corticosterone as well as a blunted fasting-induced activation of the axis. The previously described phenotypes of this animal and the reduced bone density reported here parallel those of Cushing syndrome. Thus, MC3-R is required for communicating nutritional status to both central and peripheral tissues involved in nutrient partitioning, and this defect explains much of the metabolic phenotype in the model. energy homeostasis | nonesterified fatty acid | corticotrophin-releasing hormone | hormone-sensitive lipase R esearch on the central melanocortin system has focused on the role of the melanocortin-4 receptor (MC4-R) in energy homeostasis, particularly as a result of the hyperphagic obesity syndrome found in both mice and humans with mutations in this receptor (1-3). A large body of work has demonstrated that circuitry regulated by the MC4-R is essential for much of leptin action and coordinates energy intake with energy expenditure to maintain long-term energy homeostasis (4). In contrast, the melanocortin-3 receptor (MC3-R), expressed in ∼35 different nuclei in the CNS with a pattern distinct from that of the MC4-R

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“…S-labelled UTP, as per manufacturer's instructions (Ambion). The ISHH procedure used has been described in detail previously (Alon et al, 2009;Garfield et al, 2012). Autoradiographic images were quantified using Image Proplus software (Media Cybernetics, MD 20910).…”

Section: In Situ Hybridization Histochemistry (Ishh)mentioning

confidence: 99%

“…Following this, the tissue was washed in PBS before commencement of the IHC protocol to label α-melanocyte-stimulating hormone (MSH) protein using procedures previously described (Alon et al, 2009;Garfield et al, 2012). Briefly, sections were incubated in 0.3% H2O2 in PBS, then rinsed in PBS, blocked in 0.5% BSA/ 0.5% Triton-X 100 in PBS and left in blocking buffer containing rabbit α-MSH antibody (1/10,000;…”

Section: Dual-label Ishh and Immunohistochemistry (Ihc)mentioning

confidence: 99%

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

et al. 2016

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List of abbreviations5As the prevalence of obesity increases across the globe major efforts are directed at studying the mechanisms involved. Growing evidence suggests that susceptibility to obesity can be programmed by maternal and neonatal nutrition. In particular, individuals with low birth weight that undergo rapid postnatal growth are at higher risk of developing increased adiposity in later life. The molecular mechanisms mediating the interaction between early nutrition and obesity risk are, however, still largely unknown. Currently, there are no pharmacological therapies to prevent the increase in adiposity in individuals that underwent nutritional challenge in early life. Serotonin (5-HT) system is widely recognized as one of the key regulators of food intake and body weight. During fetal life serotonin also acts as a trophic factor that regulates brain development. As compounds targeting endogenous serotonin bioavailability have been among the most clinically effective treatments for obesity (e.g. d-fenfluramine), treatment targeting serotonin system may prevent the development of obesity in at risk individuals. Results:The study has shown that maternal protein restriction increased levels of serotonin in the blood of pregnant rat mums and in the placenta and the fetal brain. In adulthood the offspring had a reduced ability to sense serotonin, which was associated with a reduced hypothalamic expression of 5-HT2Creceptors -the primary serotonin receptor influencing appetite. As expected, reduced 5-HT2Creceptor expression was associated with impaired sensitivity to serotonin-mediated appetite suppression and hence could lead to increases in food intake. On the other hand offspring of low protein dams had a programmed increase in 5-HT2A receptors, which are positioned, just like 5-HT2C receptors, in the arcuate nucleus of the hypothalamus -a key area of the brain, involved in the control of food intake. Moreover, these animals were more sensitive to 5-HT2A receptor agonistinduced appetite suppression. Implications and future directions:This study identified a molecular mechanism that is involved in mediating the effects of suboptimal maternal diet on the regulation of food intake in the offspring. In addition, the authors showed that a treatment with 5-HT2A receptor agonist may potentially prevent the development of obesity in individuals that were exposed in utero to suboptimal nutrition and then underwent rapid postnatal growth. Non-hallucinogenic 5-HT2A receptor agonist should be used for such treatment. Combining the 5-HT2A receptor agonist with 5-HT2CR and 5-HT1BR agonists could potentially further increase the anorectic therapeutic effect. Disease Models & Mechanisms • DMM • Advance article AbstractThough obesity is a global epidemic, the physiological mechanisms involved are little understood.Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low protein diet during pregnancy causes decreased intrauterine growth, rapid...

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Transgenic Mice Expressing Green Fluorescent Protein under the Control of the Corticotropin-Releasing Hormone Promoter

Cited by 62 publications

References 24 publications

An Anxiolytic Role for CRF Receptor Type 1 in the Globus Pallidus

An Anxiolytic Role for CRF Receptor Type 1 in the Globus Pallidus

Melanocortin-3 receptor regulates the normal fasting response

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

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