Proopiomelanocortin Expression in both GABA and Glutamate Neurons

Hentges, Shane T.; Otero-Corchón, Veronica; Pennock, Reagan L.; King, Connie M.; Low, Malcolm J.

doi:10.1523/jneurosci.3770-09.2009

Cited by 152 publications

(174 citation statements)

References 31 publications

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“…Both the AgRP/NPY-and POMC/CART -containing neurons contain gamma amino butyric acid (GABA) as *Address correspondence to this author at the Neuroscience Research Australia, Barker Street, Randwick, New South Wales, Australia; Tel: +61 2 9399 1128; Fax: +61 2 9399 1082; E-mail: e.gyengesi@neura.edu.au their main neurotransmitter [6][7][8][9] and project to strongly overlapping areas, including the Pa and the LH and DM [10][11][12]. POMC neurons contain GABA or glutamate [13,14], however the precise role of GABA or glutamate transmission from POMC neurons on feeding circuits remains unclear. In their recent and detailed experiments, Dicken et al, (2012) elegantly showed that besides the slow and long lasting synaptic actions typical in the case of neuropeptides, POMC neurons are also rapidly regulate both their own activity via auto regulation and the activity of downstream neurons [13,15].…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress in the Hypothalamus: the Importance of Calcium Signaling and Mitochondrial ROS in Body Weight Regulation

Gyengési¹,

Paxinos²,

Andrews³

2012

Current Neuropharmacology

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Abstract:A considerable amount of evidence shows that reactive oxygen species (ROS) in the mammalian brain are directly responsible for cell and tissue function and dysfunction. Excessive reactive oxygen species contribute to various conditions including inflammation, diabetes mellitus, neurodegenerative diseases, tumor formation, and mental disorders such as depression. Increased intracellular calcium levels have toxic roles leading to cell death. However, the exact connection between reactive oxygen production and high calcium stress is not yet fully understood. In this review, we focus on the role of reactive oxygen species and calcium stress in hypothalamic arcuate neurons controlling feeding. We revisit the role of NPY and POMC neurons in the regulation of appetite and energy homeostasis, and consider how ROS and intracellular calcium levels affect these neurons. These novel insights give a new direction to research on hypothalamic mechanisms regulating energy homeostasis and may offer novel treatment strategies for obesity and type-2 diabetes.

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Section: Introductionmentioning

confidence: 99%

Oxidative Stress in the Hypothalamus: the Importance of Calcium Signaling and Mitochondrial ROS in Body Weight Regulation

Gyengési¹,

Paxinos²,

Andrews³

2012

Current Neuropharmacology

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“…A unique feature that specifies the neuronal melanocortinergic phenotype is, in fact, the expression of Pomc because other genes necessary for POMC processing and melanocortin release are common to most other neurons expressing neuropeptide brain genes. Cotransmitters such as glutamate, GABA, or cocaineand amphetamine-regulated transcript (CART) are found only in fractions of hypothalamic POMC neurons (6,7), as are leptin, insulin, estrogen, and serotonin receptors (8)(9)(10).…”

mentioning

confidence: 99%

Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood

Nasif

Souza

González

et al. 2015

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

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Food intake and body weight regulation depend on proper expression of the proopiomelanocortin gene (Pomc) in a group of neurons located in the mediobasal hypothalamus of all vertebrates. These neurons release POMC-encoded melanocortins, which are potent anorexigenic neuropeptides, and their absence from mice or humans leads to hyperphagia and severe obesity. Although the pathophysiology of hypothalamic POMC neurons is well understood, the genetic program that establishes the neuronal melanocortinergic phenotype and maintains a fully functional neuronal POMC phenotype throughout adulthood remains unknown. Here, we report that the early expression of the LIM-homeodomain transcription factor Islet 1 (ISL1) in the developing hypothalamus promotes the terminal differentiation of melanocortinergic neurons and is essential for hypothalamic Pomc expression since its initial onset and throughout the entire lifetime. We detected ISL1 in the prospective hypothalamus just before the onset of Pomc expression and, from then on, Pomc and Isl1 coexpress. ISL1 binds in vitro and in vivo to critical homeodomain binding DNA motifs present in the neuronal Pomc enhancers nPE1 and nPE2, and mutations of these sites completely disrupt the ability of these enhancers to drive reporter gene expression to hypothalamic POMC neurons in transgenic mice and zebrafish. ISL1 is necessary for hypothalamic Pomc expression during mouse and zebrafish embryogenesis. Furthermore, conditional Isl1 inactivation from POMC neurons impairs Pomc expression, leading to hyperphagia and obesity. Our results demonstrate that ISL1 specifies the identity of hypothalamic melanocortin neurons and is required for melanocortin-induced satiety and normal adiposity throughout the entire lifespan.hypothalamus | melanocortin | obesity | Isl1 | pomc

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“…Many of these brain regions contain glutamatergic neurons (Stornetta et al 2002;Ziegler et al 2002); however, the origin of all glutamatergic inputs to the PVH has not been systemically identified. Subsets of ARC POMC neurons have been reported to express mRNA for the vesicular glutamate transporter-2 (Dicken et al 2012;Hentges et al 2009;Meister 2007;Ziegler et al 2002). Although insulin has been reported to hyperpolarize POMC neurons (Williams et al 2010), recent evidence suggests that purified insulin (without Zn in the formulation) depolarizes and excites POMC neurons (Qiu et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…First, ARC neurons express mRNA for the vesicular glutamate transporter-2 (Dicken et al 2012;Hentges et al 2009;Meister 2007;Ziegler et al 2002), and activation of ARC neurons can produce a local glutamate-mediated inward current (Hentges et al 2009). Moreover, chemical stimulation of ARC neurons increases SNA and ABP (Kawabe et al 2012a(Kawabe et al , 2012b, and this sympathoexcitatory response is converted into a sympathoinhibitory response by combined blockade of NMDA and non-NMDA receptors in the PVH (Kawabe et al 2012b).…”

mentioning

confidence: 99%

Glutamate receptors in the hypothalamic paraventricular nucleus contribute to insulin-induced sympathoexcitation

Stocker

Gordon

2015

Journal of Neurophysiology

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Stocker SD, Gordon KW. Glutamate receptors in the hypothalamic paraventricular nucleus contribute to insulin-induced sympathoexcitation. J Neurophysiol 113: 1302-1309, 2015. First published December 4, 2014 doi:10.1152/jn.00764.2014.-The sympathoexcitatory response to insulin is mediated by neurons in the arcuate nucleus (ARC) and hypothalamic paraventricular nucleus (PVH). Previous studies have reported that stimulation of ARC neurons increases sympathetic nerve activity (SNA) and arterial blood pressure (ABP) through glutamate receptor activation in the PVH. Therefore, the purpose of the present study was to determine whether glutamatergic neurotransmission in the PVH contributes to insulin-induced sympathoexcitation. Male Sprague-Dawley rats (275-400 g) were infused with isotonic saline or insulin (3.75 mU·kg Ϫ1 ·min Ϫ1 ) plus 50% dextrose to maintain euglycemia. Intravenous infusion of insulin significantly increased lumbar SNA without a significant change in mean ABP, renal SNA, heart rate, or blood glucose. Bilateral PVH injection of the excitatory amino acid antagonist kynurenic acid (KYN) lowered lumbar SNA and ABP of animals infused with insulin. Similarly, a cocktail of the NMDA antagonist DL-2-amino-5-phosphonopentanoic acid (AP5) and non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced lumbar SNA and mean ABP during infusion of insulin. In a final experiment, bilateral PVH injection of AP5 only, but not CNQX, lowered lumbar SNA and mean ABP of animals infused with insulin. The peak changes in lumbar SNA and mean ABP of insulin-treated animals were not different between KYN, AP5 plus CNQX, or AP5 alone. These drug treatments did not alter any variable in animals infused with saline. Altogether, these findings suggest that glutamatergic NMDA neurotransmission in the PVH contributes to insulin-induced sympathoexcitation.hypothalamus; lumbar; sympathetic nerve activity; NMDA; blood pressure ACCUMULATING EVIDENCE INDICATES insulin acts within the hypothalamic arcuate nucleus (ARC) to activate downstream pathways including neurons of the hypothalamic paraventricular nucleus (PVH) and rostral ventrolateral medulla (RVLM) to increase sympathetic nerve activity (SNA) and alter baroreflex function (Bardgett et al.

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Proopiomelanocortin Expression in both GABA and Glutamate Neurons

Cited by 152 publications

References 31 publications

Oxidative Stress in the Hypothalamus: the Importance of Calcium Signaling and Mitochondrial ROS in Body Weight Regulation

Oxidative Stress in the Hypothalamus: the Importance of Calcium Signaling and Mitochondrial ROS in Body Weight Regulation

Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood

Glutamate receptors in the hypothalamic paraventricular nucleus contribute to insulin-induced sympathoexcitation

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