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Mediobasal hypothalamus

Lucie Desmoulins, Chloé Chrétien, Romain Paccoud, Stephan Collins, Céline Cruciani-Guglielmacci, Anne Galinier, Fabienne Liénard, Aurore Quinault, Sylvie Grall, Camille Allard, Claire Fenech, Lionel Carneiro, Thomas Mouillot, Audren Fournel, Claude Knauf, Christophe Magnan, Xavier Fioramonti, Luc Pénicaud, Corinne Leloup
OBJECTIVE: Hypothalamic glucose sensing (HGS) initiates insulin secretion (IS) via a vagal control, participating in energy homeostasis. This requires mitochondrial reactive oxygen species (mROS) signaling, dependent on mitochondrial fission, as shown by invalidation of the hypothalamic DRP1 protein. Here, our objectives were to determine whether a model with a HGS defect induced by a short, high fat-high sucrose (HFHS) diet in rats affected the fission machinery and mROS signaling within the mediobasal hypothalamus (MBH)...
November 27, 2018: Molecular Metabolism
Leticia E Sewaybricker, Ellen A Schur, Susan J Melhorn, Brunno M Campos, Mary K Askren, Guilherme A S Nogueira, Mariana P Zambon, Maria Angela R G M Antonio, Fernando Cendes, Licio A Velloso, Gil Guerra-Junior
OBJECTIVE: In adults, hypothalamic gliosis has been documented using quantitative T2 neuroimaging, whereas functional magnetic resonance imaging (fMRI) has shown a defective hypothalamic response to nutrients. No studies have yet evaluated these hypothalamic abnormalities in children with obesity. METHODS: Children with obesity and lean controls underwent quantitative MRI measuring T2 relaxation time, along with continuous hypothalamic fMRI acquisition to evaluate early response to glucose ingestion...
December 10, 2018: Pediatric Obesity
Kathryn E Berkseth, Katya B Rubinow, Susan J Melhorn, Mary F Webb, Mary Rosalynn B De Leon, Brett T Marck, Alvin M Matsumoto, John K Amory, Stephanie T Page, Ellen A Schur
OBJECTIVE: This study aimed to determine whether a relationship was evident between gliosis in the mediobasal hypothalamus (MBH) and plasma testosterone concentrations in men. METHODS: A total of 41 adult men (aged 18-50 years) from 23 twin pairs underwent fasting morning blood draw and brain magnetic resonance imaging. T2 relaxation time was used to quantify gliosis in the MBH and control areas in the putamen and amygdala. Plasma concentrations of testosterone and 17β-estradiol were measured by liquid chromatography-tandem mass spectrometry...
December 2018: Obesity
Mary K Herrick, Kristin M Favela, Richard B Simerly, Naji N Abumrad, Nathan C Bingham
BACKGROUND: Exposure of rodents to chronic high-fat diet (HFD) results in upregulation of inflammatory markers and proliferation of microglia within the mediobasal hypothalamus. Such hypothalamic inflammation is associated with metabolic dysfunction, central leptin resistance, and maintenance of obesity. Bariatric surgeries result in long-term stable weight loss and improved metabolic function. However, the effects of such surgical procedures on HFD-induced hypothalamic inflammation are unknown...
October 24, 2018: Molecular Medicine
Yusuke Nakane, Takashi Yoshimura
Organisms use changes in photoperiod for seasonal reproduction to maximize the survival of their offspring. Birds have sophisticated seasonal mechanisms and are therefore excellent models for studying these phenomena. Birds perceive light via deep-brain photoreceptors and long day-induced thyroid-stimulating hormone (TSH, thyrotropin) in the pars tuberalis of the pituitary gland (PT), which cause local thyroid hormone activation within the mediobasal hypothalamus. The local bioactive thyroid hormone controls seasonal gonadotropin-releasing hormone secretion and subsequent gonadotropin secretion...
October 17, 2018: Annual Review of Animal Biosciences
Oscar A Brown, Martina Canatelli-Mallat, Gloria M Console, Gisela Camihort, Georgina Luna, Eduardo Spinedi, Rodolfo G Goya
BACKGROUND: Insulin-like growth factor1 (IGF1) is a powerful neuroprotective molecule. We have previously shown that short-term hypothalamic IGF1 gene therapy restores tuberoinfundibular dopaminergic neuron function in aging female rats. OBJECTIVE: Our aim was to implement long-term IGF-I gene therapy in pituitary prolactinomas in senile female rats. METHODS: Here, we assessed the long-term effect of IGF1 gene therapy in the hypothalamus of young (4 mo...
September 5, 2018: Current Gene Therapy
Niloy Jafar Iqbal, Zhonglei Lu, Shun Mei Liu, Gary J Schwartz, Streamson Chua, Liang Zhu
When obesity is caused by consumption of a high-fat diet, the tumor suppressor pRb is phosphoinactivated in the neurons of the mediobasal hypothalamus, a brain area critical for energy-balance regulation. However, the functional relevance of pRb phosphoinactivation in the mediobasal hypothalamus to diet-induced obesity remains unknown. Here, we show that inhibiting pRb phosphorylation in the mediobasal hypothalamus can prevent and treat diet-induced obesity in mice. Expressing an unphosphorylable pRb nonselectively in the mediobasal hypothalamus or conditionally in anorexigenic POMC neurons inhibits diet-induced obesity...
September 6, 2018: JCI Insight
Peyton W Weems, Lique M Coolen, Stanley M Hileman, Steven Hardy, Rick B McCosh, Robert L Goodman, Michael N Lehman
A subpopulation of neurons located within the arcuate nucleus, colocalizing kisspeptin, neurokinin B, and dynorphin (Dyn; termed KNDy neurons), represents key mediators of pulsatile GnRH secretion. The KNDy model of GnRH pulse generation proposes that Dyn terminates each pulse. However, it is unknown where and when during a pulse that Dyn is released to inhibit GnRH secretion. Dyn acts via the κ opioid receptor (KOR), and KOR is present in KNDy and GnRH neurons in sheep. KOR, similar to other G protein-coupled receptors, are internalized after exposure to ligand, and thus internalization can be used as a marker of endogenous Dyn release...
September 1, 2018: Endocrinology
Michelle N Bedenbaugh, Richard B McCosh, Justin A Lopez, John M Connors, Robert L Goodman, Stanley M Hileman
BACKGROUND: Neuronal intermediates that communicate estrogen and progesterone feedback to gonadotropin-releasing hormone (GnRH) neurons are essential for modulating reproductive cyclicity. Individually, kisspeptin and nitric oxide (NO) influence GnRH secretion. However, it is possible these 2 neuronal intermediates interact with one another to affect reproductive cyclicity. METHODS: We investigated the neuroanatomical relationship of one isoform of the enzyme that synthesizes NO, neuronal NO synthase (nNOS), to kisspeptin and GnRH in adult female rhesus monkeys and sheep using dual-label immunofluorescence...
2018: Neuroendocrinology
Guadalupe Navarro, Camille Allard, Jamie J Morford, Weiwei Xu, Suhuan Liu, Adrien Jr Molinas, Sierra M Butcher, Nicholas HF Fine, Manuel Blandino-Rosano, Venkata N Sure, Sangho Yu, Rui Zhang, Heike Münzberg, David A Jacobson, Prasad V Katakam, David J Hodson, Ernesto Bernal-Mizrachi, Andrea Zsombok, Franck Mauvais-Jarvis
Androgen excess predisposes women to type 2 diabetes (T2D), but the mechanism of this is poorly understood. We report that female mice fed a Western diet and exposed to chronic androgen excess using dihydrotestosterone (DHT) exhibit hyperinsulinemia and insulin resistance associated with secondary pancreatic β cell failure, leading to hyperglycemia. These abnormalities are not observed in mice lacking the androgen receptor (AR) in β cells and partially in neurons of the mediobasal hypothalamus (MBH) as well as in mice lacking AR selectively in neurons...
June 21, 2018: JCI Insight
C L Tan, P W Sheard, C L Jasoni
Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are required for fertility in all mammalian species studied to date. GnRH neuron cell bodies reside in the basal forebrain, and most extend long neurites in the caudal direction to terminate at the median eminence (ME), the site of hormone secretion. Using in vitro neurite growth assays, histological methods, and genetic deletion strategies in mice we have analysed the role of the morphogen and neurite growth and guidance molecule, Sonic hedgehog (Shh), in the growth of GnRH neurites to their target...
May 19, 2018: International Journal of Developmental Neuroscience
Panida Loutchanwoot, Tina Vortherms
Effects of puerarin on the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator function is investigated, for the first time, in ovariectomized rats at the level of mRNA expression of estrogen-responsive genes, e.g., estrogen receptor (ER), GnRH and its receptor (GnRHR). Rats were treated orally for 90 days either with a soy-free diet containing two different doses of puerarin (low dose of 600 mg/kg and high dose of 3000 mg/kg) or estradiol benzoate (E2B) at either low dose (4.3 mg/kg) or high dose (17...
July 2018: Steroids
Natália F Mendes, Joana M Gaspar, José C Lima-Júnior, Jose Donato, Lício A Velloso, Eliana P Araújo
BACKGROUND: The consumption of large amounts of dietary fats induces hypothalamic inflammation and impairs the function of the melanocortin system, leading to a defective regulation of caloric intake and whole-body energy expenditure. In mice fed a high-fat diet (HFD), TGF-β1 expression was increased and NF-κB signaling was activated in proopiomelanocortin neurons, which plays an important role in the obesity-associated hypothalamic inflammation scenario. However, whether excessive hypothalamic TGF-β1 impairs energy homeostasis remains unclear...
August 2018: Metabolism: Clinical and Experimental
Elise Laperrousaz, Raphaël G Denis, Nadim Kassis, Cristina Contreras, Miguel López, Serge Luquet, Céline Cruciani-Guglielmacci, Christophe Magnan
Lipoprotein lipase (LPL) is expressed in different areas of the brain, including the hypothalamus and plays an important role in neural control of the energy balance, including feeding behavior and metabolic fluxes. This study tested the hypothesis that hypothalamic LPL participates in the control of body temperature. We first showed that cold exposure induces decreased activity and expression of LPL in the mouse hypothalamus. We then selectively deleted LPL in the mediobasal hypothalamus (MBH) through an adeno-associated virus approach in LPL-floxed mice and generated MBHΔ Lpl mice with 30-35% decrease in hypothalamic LPL activity...
2018: Frontiers in Endocrinology
Laszlo Biro, Eszter Sipos, Biborka Bruzsik, Imre Farkas, Dora Zelena, Diana Balazsfi, Mate Toth, Jozsef Haller
An important question in behavioral neurobiology is how particular neuron populations and pathways mediate the overall roles of brain structures. Here we investigated this issue by studying the medial prefrontal cortex (mPFC), an established locus of inhibitory control of aggression. We established in male rats that dominantly distinct mPFC neuron populations project to and produce dense fiber networks with glutamate release sites in the mediobasal hypothalamus (MBH) and lateral hypothalamus (LH; i.e., two executory centers of species-specific and violent bites, respectively)...
April 25, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
M Szlis, J Polkowska, E Skrzeczyńska, B J Przybył, A Wójcik-Gładysz
The participation of peripheral peptides in the processes regulating the food intake (energy homeostasis) at the central nervous system level remains unclear. This study focuses on the role of obestatin in neuronal activity within the hypothalamic appetite-regulating network in ruminants. The animals (n = 28) were randomly divided into two groups. The sheep in the control group received intracerebroventricular infusions of the Ringer-Locke solution, and the sheep in obestatin group were infused with obestatin (diluted in the Ringer-Locke solution) at 25 μg per 120 μl/hr...
June 2018: Journal of Animal Physiology and Animal Nutrition
Nicholas Heeley, Peter Kirwan, Tamana Darwish, Marion Arnaud, Mark L Evans, Florian T Merkle, Frank Reimann, Fiona M Gribble, Clemence Blouet
OBJECTIVE: Dietary proteins are sensed by hypothalamic neurons and strongly influence multiple aspects of metabolic health, including appetite, weight gain, and adiposity. However, little is known about the mechanisms by which hypothalamic neural circuits controlling behavior and metabolism sense protein availability. The aim of this study is to characterize how neurons from the mediobasal hypothalamus respond to a signal of protein availability: the amino acid l-leucine. METHODS: We used primary cultures of post-weaning murine mediobasal hypothalamic neurons, hypothalamic neurons derived from human induced pluripotent stem cells, and calcium imaging to characterize rapid neuronal responses to physiological changes in extracellular l-Leucine concentration...
April 2018: Molecular Metabolism
Aleisha M Moore, Kathryn A Lucas, Robert L Goodman, Lique M Coolen, Michael N Lehman
Kisspeptin/Neurokinin B/Dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in the regulation of fertility. The ability to detect features of KNDy neurons that are essential for fertility may require three-dimensional (3D) imaging of the complete population. Recently developed protocols for optical tissue clearing permits 3D imaging of neuronal populations in un-sectioned brains. However, these techniques have largely been described in the mouse brain. We report 3D imaging of the KNDy cell population in the whole rat brain and sheep hypothalamus using immunolabelling and modification of a solvent-based clearing protocol, iDISCO...
February 2, 2018: Scientific Reports
Szabolcs Takács, Zsuzsanna Bardóczi, Katalin Skrapits, Balázs Göcz, Viktória Váczi, Zsófia Maglóczky, Iván Szűcs, Gergely Rácz, András Matolcsy, Waljit S Dhillo, Masahiko Watanabe, Andrea Kádár, Csaba Fekete, Imre Kalló, Erik Hrabovszky
Kisspeptin (KP) synthesizing neurons of the hypothalamic infundibular region are critically involved in the central regulation of fertility; these cells regulate pulsatile gonadotropin-releasing hormone (GnRH) secretion and mediate sex steroid feedback signals to GnRH neurons. Fine structural analysis of the human KP system is complicated by the use of post mortem tissues. To gain better insight into the neuroanatomy of the somato-dendritic cellular compartment, we introduced the diolistic labeling of immunohistochemically identified KP neurons using a gene gun loaded with the lipophilic dye, DiI...
June 2018: Brain Structure & Function
Joseph Polex-Wolf, Brian Yh Lam, Rachel Larder, John Tadross, Debra Rimmington, Fàtima Bosch, Verónica Jiménez Cenzano, Eduard Ayuso, Marcella Kl Ma, Kara Rainbow, Anthony P Coll, Stephen O'Rahilly, Giles Sh Yeo
Profound hyperphagia is a major disabling feature of Prader-Willi syndrome (PWS). Characterization of the mechanisms that underlie PWS-associated hyperphagia has been slowed by the paucity of animal models with increased food intake or obesity. Mice with a microdeletion encompassing the Snord116 cluster of noncoding RNAs encoded within the Prader-Willi minimal deletion critical region have previously been reported to show growth retardation and hyperphagia. Here, consistent with previous reports, we observed growth retardation in Snord116+/-P mice with a congenital paternal Snord116 deletion...
March 1, 2018: Journal of Clinical Investigation
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