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Mediobasal hypothalamus

Lidia I Serova, Chiso Nwokafor, Elisabeth J Van Bockstaele, Beverly A S Reyes, Xiaoping Lin, Esther L Sabban
PTSD is heterogeneous disorder that can be long lasting and often has delayed onset following exposure to a traumatic event. Therefore, it is important to take a staging approach to evaluate progression of biological mechanisms of the disease. Here, we begin to evaluate the temporal trajectory of changes following exposure to traumatic stressors in the SPS rat PTSD model. The percent of animals displaying severe anxiety on EPM increased from 17.5% at one week to 57.1% two weeks after SPS stressors, indicating delayed onset or progressive worsening of the symptoms...
March 13, 2019: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Vruti Patel, Guillaume Bidault, Joseph E Chambers, Stefania Carobbio, Angharad J T Everden, Concepción Garcés, Lucy E Dalton, Fiona M Gribble, Antonio Vidal-Puig, Stefan J Marciniak
Phosphorylation of the translation initiation factor eIF2α within the mediobasal hypothalamus is known to suppress food intake, but the role of the eIF2α phosphatases in regulating body weight is poorly understood. Mice deficient in active PPP1R15A, a stress-inducible eIF2α phosphatase, are healthy and more resistant to endoplasmic reticulum stress than wild type controls. We report that when female Ppp1r15a mutant mice are fed a high fat diet they gain less weight than wild type littermates owing to reduced food intake...
February 27, 2019: Scientific Reports
Presheet P Patkar, Zheng Hao, Michael B Mumphrey, R Leigh Townsend, Hans-Rudolf Berthoud, Andrew C Shin
OBJECTIVES: Dieting often fails because weight loss triggers strong counter-regulatory biological responses such as increased hunger and hypometabolism that are thought to be critically dependent on the master fuel sensor in the mediobasal hypothalamus (MBH). Because prolonged starvation has been shown to increase AgRP and NPY, the expression level of these two orexigenic genes has been taken as an experimental readout for the presence or absence of hunger. Roux-en-Y gastric bypass (RYGB) surgery leads to a significant weight loss without inducing the associated hunger, indicating possible changes in hypothalamic neuropeptides and/or signaling...
February 4, 2019: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Yanira Santana, Angel L Montejo, Javier Martín, Ginés LLorca, Gloria Bueno, Juan Luis Blázquez
Antidepressant-related sexual dysfunction is a frequent adverse event caused by serotonergic activation that intensely affects quality of life and adherence in depressed patients. The dopamine system has multiple effects promoting sexual behavior, but no studies have been carried out to confirm dopaminergic changes involved in animal models after antidepressant use. METHODS: The sexual behavior-related dopaminergic system in the rat was studied by comparing two different antidepressants and placebo for 28 days...
January 23, 2019: Journal of Clinical Medicine
Bruna Bombassaro, Albina F S Ramalho, Milena Fioravante, Carina Solon, Guilherme Nogueira, Pedro A S Nogueira, Rodrigo S Gaspar, Eduardo R Ropelle, Licio A Velloso
Obesity-associated hypothalamic inflammation plays an important role in the development of defective neuronal control of whole body energy balance. Because dietary fats are the main triggers of hypothalamic inflammation, we hypothesized that CD1, a lipid-presenting protein, may be involved in the hypothalamic inflammatory response in obesity. Here, we show that early after the introduction of a high-fat diet, CD1 expressing cells gradually appear in the mediobasal hypothalamus. The inhibition of hypothalamic CD1 reduces diet-induced hypothalamic inflammation and rescues the obese and glucose-intolerance phenotype of mice fed a high-fat diet...
January 17, 2019: Brain, Behavior, and Immunity
Anna Wójcik-Gładysz, Michał Szlis, Bartosz Jarosław Przybył, Jolanta Polkowska
The effects of obestatin on gonadotrophic axis activity in ruminants have not yet been determined. The aim of this study was to investigate the effect of intracerebroventricular infusions of obestatin on the gonadotrophin-releasing hormone (GnRH) mRNA and protein expressions as well as on KNDy mRNA and kisspeptin (Kiss) peptide expressions in peripubertal female sheep. Animals were randomly divided into two groups: the control group received intracerebroventricular infusions of the vehicle, and the obestatin group was infused with obestatin (25 μg/120 μL h-1 )...
December 19, 2018: Research in Veterinary Science
Cristina Sáenz de Miera
Seasonal rhythms in physiology are widespread among mammals living in temperate zones. These rhythms rely on the external photoperiodic signal to be entrained to the seasons, but persist under constant conditions, revealing their endogenous origin. Internal long-term timing (circannual cycles) can be revealed in the lab as photoperiodic-history dependent responses - i.e. the ability to respond differently to similar photoperiodic cues based on prior photoperiodic experience. In juveniles, history-dependence relies on the photoperiod transmitted by the mother to the fetus in utero, a phenomenon known as "maternal photoperiodic programming" (MPP)...
December 26, 2018: Journal of Neuroendocrinology
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
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