Hypocretin/Orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: Relationship to the neuropeptide Y and agouti gene-related protein systems

Broberger, Christian; Lecea, Luı́s de; Sutcliffe, J. Gregor; Hökfelt, Tomas

doi:10.1002/(sici)1096-9861(19981228)402:4<460::aid-cne3>3.0.co;2-s

Cited by 642 publications

(371 citation statements)

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“…70 One of the POMC products, adrenocorticotropic hormone, is secreted by the anterior pituitary and stimulates adrenocortical cells. In the CNS, POMC neurons are localized in two sites in rodents and humans, the Arc (Figure 2a, c) 71,72 and the nucleus of the solitary tract (NTS). 70 Currently, considerable attention has focused on another POMC product, a-melanocyte-stimulating hormone (a-MSH).…”

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“…[92][93][94] Interestingly, AgRP is produced exclusively in the Arc in rodents, monkeys, and humans. 71,72,[93][94][95][96][97] Alpha-MSH-producing (Figure 2a, c) and AgRP-producing (Figure 3c, e) neurons are distributed and segregated in the medial and lateral regions of the Arc, respectively. 71,72 In line with the results from the aforementioned molecular genetic studies on the MC4-R, transgenic overexpression of AgRP produces obesity.…”

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“…71,72,[93][94][95][96][97] Alpha-MSH-producing (Figure 2a, c) and AgRP-producing (Figure 3c, e) neurons are distributed and segregated in the medial and lateral regions of the Arc, respectively. 71,72 In line with the results from the aforementioned molecular genetic studies on the MC4-R, transgenic overexpression of AgRP produces obesity. 93,94 In contrast to POMC mRNA, AgRP mRNA is increased in leptindeficient ob/ob mice and leptin-resistant db/db mice, and during periods of fasting when leptin levels rapidly fall.…”

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confidence: 99%

“…97,98 Finally, it is important to note that AgRP is coexpressed with NPY in the Arc (see the section 'the NPY/Y1-receptor system'). 71 (also applied to (a)), 200 mm in (d) (also applied to (c)), 100 mm in (f) (also applied to (e)). ARC, arcuate nucleus; fx, fornix; ot, optic tract; 3v, third ventricle.…”

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“…Melanocortin neurons project to MC4-R-positive CNS sites involved in regulating food intake and body weight Despite the very limited distribution of POMC and AgRP cells bodies, 71,72,106 their axonal projections are widespread across the CNS. Several immunohistochemical studies have demonstrated CNS distributions of a-MSH-positive and AgRP-positive axons in rodents, monkeys, and humans.…”

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Body weight is regulated by the brain: a link between feeding and emotion

2005

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Regulated energy homeostasis is fundamental for maintaining life. Unfortunately, this critical process is affected in a high number of mentally ill patients. Eating disorders such as anorexia nervosa are prevalent in modern societies. Impaired appetite and weight loss are common in patients with depression. In addition, the use of neuroleptics frequently produces obesity and diabetes mellitus. However, the neural mechanisms underlying the pathophysiology of these behavioral and metabolic conditions are largely unknown. In this review, we first concentrate on the established brain machinery of food intake and body weight, especially on the melanocortin and neuropeptide Y (NPY) systems as illustration. These systems play a critical role in receiving and processing critical peripheral metabolic cues such as leptin and ghrelin. It is also notable that both systems modulate emotion and motivated behavior as well. Secondly, we discuss the significance and potential promise of multidisciplinary molecular and neuroanatomic techniques that will likely increase the understanding of brain circuitries coordinating energy homeostasis and emotion. Finally, we introduce several lines of evidence suggesting a link between the melanocortin/NPY systems and several neurotransmitter systems on which many of the psychotropic agents exert their influence. Maintaining energy homeostasis is fundamental for survival. However, obesity due to over-nutrition is an increasing worldwide public health problem. 1 In psychiatric practice, on the other hand, impaired appetite is one of the crucial issues. Anorexia and weight loss are common, for example, in patients suffering from depression. Eating disorders are medically intractable and life threatening. In addition, the so-called 'atypical' antipsychotic agents, currently and widely used to treat psychoses, often induce hyperphagia, obesity, and diabetes mellitus. [2][3][4] In the past decade, fortunately, there has been remarkable progress in understanding the molecular mechanisms of food intake and body weight. This is due in large part to increased research activity towards combating the rising incidences of obesity and associated metabolic disorders. As a result, it is now established that the central nervous system (CNS) senses and processes peripheral metabolic cues including leptin 5 and ghrelin, 6,7 resulting in coordinated energy homeostasis. However, the pathophysiology of the disequilibrium between energy intake and expenditure in psychiatric disorders remains largely unknown. Nevertheless, evidence suggests that several CNS systems regulating energy balance may be dysregulated in patients with mental illnesses, for example, eating disorders, and drug addiction. [8][9][10][11][12][13][14] In the current review, we will illustrate the neuroanatomic and molecular genetic aspects of the melanocortin and neuropeptide Y (NPY) systems residing in the CNS downstream of leptin and ghrelin, to discuss the neural bases of feeding, metabolism, and emotion. Additionally, we point the reader to...

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Body weight is regulated by the brain: a link between feeding and emotion

2005

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Toward a new neurobiology of energy balance, appetite, and obesity: The anatomists weigh in

Sawchenko

1998

J. Comp. Neurol.

232

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Organisation of the cortical projection to the zona incerta of the thalamus

Mitrofanis

Mikuletic

1999

J. Comp. Neurol.

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In this study, we examined the organisation of the cortical projection to a small nucleus of the ventral thalamus called the zona incerta. Injections of biotinylated dextran were made into various cytoarchitectonically defined cortical areas of Sprague‐Dawley rats, including the frontal (Fr1), cingulate (Cg1), parietal (Par1), forelimb (FL), and occipital (Oc1), and the patterns of anterograde labelling were examined in the zona incerta. In addition, injections of cholera toxin subunit B (CTB) were made into the zona incerta itself, and the laminar locations of retrogradely labelled cells were examined. Brains were then fixed in aldehyde and processed by using standard methods. After injections of dextran into the different cortical areas, the distribution and number of labelled terminals in the zona incerta were quite different. In terms of number, Cg1 had the heaviest projection to the zona incerta, whereas Oc1 had the weakest. In terms of distribution, three distinct patterns were evident. Firstly, labelled terminals were seen in distinct clusters in the dorsal and ventral sectors, usually one overlying the other (Fr1, FL, Par1). Secondly, labelled terminals were seen occupying much broader zones in the dorsal (and rostral) sector (Cg1). Thirdly, very few labelled terminals were seen in any incertal sector (Oc1). Thus, these results suggest that not all cortical areas project to the zona incerta equally, with some areas having stronger projections to this nucleus than others. From our CTB injections into the zona incerta itself, we show that all retrogradely labelled cells in the neocortex were limited to layer V. We suggest a possible thalamic circuit involving the zona incerta, the thalamic reticular nucleus (the other major nucleus of the ventral thalamus), and the two types of corticothalamic afferents (from layer VI and V). J. Comp. Neurol. 412:173–185, 1999. © 1999 Wiley‐Liss, Inc.

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Hypocretin/Orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: Relationship to the neuropeptide Y and agouti gene-related protein systems

Cited by 642 publications

References 57 publications

Body weight is regulated by the brain: a link between feeding and emotion

Body weight is regulated by the brain: a link between feeding and emotion

Toward a new neurobiology of energy balance, appetite, and obesity: The anatomists weigh in

Organisation of the cortical projection to the zona incerta of the thalamus

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