The melanocortin-3 receptor is a pharmacological target for the regulation of anorexia

2021 ◽  
Vol 13 (590) ◽  
pp. eabd6434
Author(s):  
Patrick Sweeney ◽  
Michelle N. Bedenbaugh ◽  
Jose Maldonado ◽  
Pauline Pan ◽  
Katelyn Fowler ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Feeding Behavior ◽  
Critical Role ◽  
Brain Regions ◽  
Sexually Dimorphic ◽  
Male And Female ◽  
Female Mice ◽  
Bidirectional Regulation ◽  
Fear And Anxiety ◽  
Agouti Related Protein

Ablation of hypothalamic AgRP (Agouti-related protein) neurons is known to lead to fatal anorexia, whereas their activation stimulates voracious feeding and suppresses other motivational states including fear and anxiety. Despite the critical role of AgRP neurons in bidirectionally controlling feeding, there are currently no therapeutics available specifically targeting this circuitry. The melanocortin-3 receptor (MC3R) is expressed in multiple brain regions and exhibits sexual dimorphism of expression in some of those regions in both mice and humans. MC3R deletion produced multiple forms of sexually dimorphic anorexia that resembled aspects of human anorexia nervosa. However, there was no sexual dimorphism in the expression of MC3R in AgRP neurons, 97% of which expressed MC3R. Chemogenetic manipulation of arcuate MC3R neurons and pharmacologic manipulation of MC3R each exerted potent bidirectional regulation over feeding behavior in male and female mice, whereas global ablation of MC3R-expressing cells produced fatal anorexia. Pharmacological effects of MC3R compounds on feeding were dependent on intact AgRP circuitry in the mice. Thus, the dominant effect of MC3R appears to be the regulation of the AgRP circuitry in both male and female mice, with sexually dimorphic sites playing specialized and subordinate roles in feeding behavior. Therefore, MC3R is a potential therapeutic target for disorders characterized by anorexia, as well as a potential target for weight loss therapeutics.

scholarly journals Can quantifying morphology and TMEM119 expression distinguish between microglia and infiltrating macrophages after ischemic stroke and reperfusion in male and female mice?

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Kimberly F. Young ◽  
Rebeca Gardner ◽  
Victoria Sariana ◽  
Susan A. Whitman ◽  
Mitchell J. Bartlett ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Western Blot ◽  
Calcium Binding ◽  
Transmembrane Protein ◽  
Brain Regions ◽  
Morphological Data ◽  
Cell Populations ◽  
Male And Female ◽  
Female Mice

AbstractBackgroundIschemic stroke is an acquired brain injury with gender-dependent outcomes. A persistent obstacle in understanding the sex-specific neuroinflammatory contributions to ischemic brain injury is distinguishing between resident microglia and infiltrating macrophages—both phagocytes—and determining cell population-specific contributions to injury evolution and recovery processes. Our purpose was to identify microglial and macrophage populations regulated by ischemic stroke using morphology analysis and the presence of microglia transmembrane protein 119 (TMEM119). Second, we examined sex and menopause differences in microglia/macrophage cell populations after an ischemic stroke.MethodsMale and female, premenopausal and postmenopausal, mice underwent either 60 min of middle cerebral artery occlusion and 24 h of reperfusion or sham surgery. The accelerated ovarian failure model was used to model postmenopause. Brain tissue was collected to quantify the infarct area and for immunohistochemistry and western blot methods. Ionized calcium-binding adapter molecule, TMEM119, and confocal microscopy were used to analyze the microglia morphology and TMEM119 area in the ipsilateral brain regions. Western blot was used to quantify protein quantity.ResultsPost-stroke injury is increased in male and postmenopause female mice vs. premenopause female mice (p< 0.05) with differences primarily occurring in the caudal sections. After stroke, the microglia underwent a region, but not sex group, dependent transformation into less ramified cells (p< 0.0001). However, the number of phagocytic microglia was increased in distal ipsilateral regions of postmenopausal mice vs. the other sex groups (p< 0.05). The number of TMEM119-positive cells was decreased in proximity to the infarct (p< 0.0001) but without a sex group effect. Two key findings prevented distinguishing microglia from systemic macrophages. First, morphological data were not congruent with TMEM119 immunofluorescence data. Cells with severely decreased TMEM119 immunofluorescence were ramified, a distinguishing microglia characteristic. Second, whereas the TMEM119 immunofluorescence area decreased in proximity to the infarcted area, the TMEM119 protein quantity was unchanged in the ipsilateral hemisphere regions using western blot methods.ConclusionsOur findings suggest that TMEM119 is not a stable microglia marker in male and female mice in the context of ischemic stroke. Until TMEM119 function in the brain is elucidated, its use to distinguish between cell populations following brain injury with cell infiltration is cautioned.

scholarly journals Performance, but not size, of hindleg weaponry is sexually dimorphic in the giant mesquite bug (Thasus neocalifornicus)

2020 ◽  
Author(s):  
Zackary A. Graham ◽  
Nicole Kaiser ◽  
Alexandre V. Palaoro
Keyword(s):  
Sexual Dimorphism ◽  
Muscle Mass ◽  
Sexually Dimorphic ◽  
Aggressive Interaction ◽  
Body Parts ◽  
Single Measure ◽  
Male And Female ◽  
Aggressive Interactions ◽  
Sexual Dimorphisms

ABSTRACTIn many species, males possess specialized weaponry that have evolved to confer a benefit during aggressive interactions. Because male weaponry is typically an exaggerated or extreme version of pre-existing body parts, females often possess reduced or weaponry. Although much research has investigated sexual dimorphism in the sizes of such weapons, other weapon components, such as weapon performance or alternative weapon forms can also explain the evolution of weapon sexual dimorphisms. Here, we investigated the allometry and variation of multiple weapon components of hindleg weaponry in the male and female giant mesquite bugs, Thasus necalifornicus. Despite theory predicating greater allocation in male weaponry, we found that females allocated more into the lengths of their hindlegs compared to males. Despite this allocation, males possess relatively wider hindlegs, which likely increase area of muscle mass. Indeed, the squeezing performance of male hindlegs was much greater than that of female hindlegs. Lastly, we also described the allometry and variation in a male weapon component, prominent tibial spines, which likely are used to damage competitors during aggressive interaction. Overall, our findings highlight the intricacies of weapon sexual dimorphism and demonstrate the importance of measuring multiple weapon components and not a single measure.

scholarly journals Sexually Dimorphic Response of Increasing Dietary Intake of High Amylose Wheat on Metabolic and Reproductive Outcomes in Male and Female Mice

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 61
Author(s):  
See Meng Lim ◽  
Amanda J. Page ◽  
Hui Li ◽  
John Carragher ◽  
Iain Searle ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Fat Mass ◽  
Fasting Blood Glucose ◽  
Abdominal Circumference ◽  
Sexually Dimorphic ◽  
Reproductive Parameters ◽  
Male And Female ◽  
Female Mice ◽  
Testicular Weight ◽  
High Amylose

High amylose wheat (HAW) has a higher resistant starch content and lower glycaemic index than standard amylose wheat (SAW), which may be associated with health benefits. This study aimed to determine the effects of replacing SAW with HAW on metabolic and reproductive parameters in male and female mice. Male and female C57BL/6 mice were randomly divided into groups (n = 8/group/sex) and fed either a SAW65 (65% SAW w/w; control), HAW35 (35% HAW w/w), HAW50 (50% HAW w/w) or HAW65 (65% HAW w/w) diet for eight weeks. In male but not female, the HAW65 group had a lower abdominal circumference, relative total fat mass, relative gonadal fat mass and plasma leptin concentration compared to the HAW35 group. There were no differences in fasting blood glucose concentrations or plasma concentrations of cholesterol, triglycerides or non-esterified fatty acids between groups in either males or females. The HAW-fed males had a higher testicular weight and HAW-fed females spent less time in diestrus and a longer time in metestrus compared to the SAW-fed mice. Higher dietary intake of HAW appears to reduce abdominal fat deposition compared to the lower level of HAW in a sexually dimorphic manner. The impacts on reproductive parameters in the HAW-fed mice require further investigation.

scholarly journals Behavioral Deficits and Brain α-Synuclein and Phosphorylated Serine-129 α-Synuclein in Male and Female Mice Overexpressing Human α-Synuclein

2020 ◽  
pp. 1-19
Author(s):  
Lilit Gabrielyan ◽  
Honghui Liang ◽  
Artem Minalyan ◽  
Asa Hatami ◽  
Varghese John ◽  
...  
Keyword(s):  
Lewy Bodies ◽  
Distribution Patterns ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Nigrostriatal System ◽  
Brain Areas ◽  
Male And Female ◽  
Female Mice ◽  
Motor Behaviors ◽  
Lateral Parabrachial Nucleus

Background: Alpha-synuclein (α-syn) is a molecule involved in pathology of Parkinson’s disease, and 90%of α-syn in Lewy bodies is phosphorylated at serine 129 (pS129 α-syn). Objective: To assess motor and non-motor behaviors in male and female mice overexpressing human α-syn under Thy1 promoter (Thy1-α-syn) and wild type (wt) littermates. Methods: Motor and non-motor behaviors brain human α-syn levels by ELISA, and mapped α-syn and pS129 α-syn in the brain by immunohistochemistry. Results: Male and female wt littermates did not show differences in the behavioral tests. Male Thy1-α-syn mice displayed more severe impairments than female counterparts in cotton nesting, pole tests, adhesive removal, finding buried food, and marble burying. Concentrations of human α-syn in the olfactory regions, cortex, nigrostriatal system, and dorsal medulla were significantly increased in Thy1-α-syn mice, higher in males than females. Immunoreactivity of α-syn was not simply increased in Thy1-α-syn mice but had altered localization in somas and fibers in a few brain areas. Abundant pS129 α-syn existed in many brain areas of Thy1-α-syn mice, while there was none or only a small amount in a few brain regions of wt mice. The substantia nigra, olfactory regions, amygdala, lateral parabrachial nucleus, and dorsal vagal complex displayed different distribution patterns between wt and transgenic mice, but not between sexes. Conclusion: The severer abnormal behaviors in male than female Thy1-α-syn mice may be related to higher brain levels of human α-syn, in the absence of sex differences in the altered brain immunoreactivity patterns of α-syn and pS129 α-syn.

scholarly journals Gonad-related factors promote muscle performance gain during postnatal development in male and female mice

2017 ◽  
Vol 313 (1) ◽  
pp. E12-E25 ◽  
Author(s):  
Vanessa Ueberschlag-Pitiot ◽  
Amalia Stantzou ◽  
Julien Messéant ◽  
Megane Lemaitre ◽  
Daniel J. Owens ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Postnatal Development ◽  
Muscle Fiber ◽  
Muscle Performance ◽  
Performance Gain ◽  
Related Factors ◽  
Muscle Weight ◽  
Male And Female ◽  
Female Mice ◽  
Muscle Contractile

To better define the role of male and female gonad-related factors (MGRF, presumably testosterone, and FGRF, presumably estradiol, respectively) on mouse hindlimb skeletal muscle contractile performance/function gain during postnatal development, we analyzed the effect of castration initiated before puberty in male and female mice. We found that muscle absolute and specific (normalized to muscle weight) maximal forces were decreased in 6-mo-old male and female castrated mice compared with age- and sex-matched intact mice, without alteration in neuromuscular transmission. Moreover, castration decreased absolute and specific maximal powers, another important aspect of muscle performance, in 6-mo-old males, but not in females. Absolute maximal force was similarly reduced by castration in 3-mo-old muscle fiber androgen receptor (AR)-deficient and wild-type male mice, indicating that the effect of MGRF was muscle fiber AR independent. Castration reduced the muscle weight gain in 3-mo mice of both sexes and in 6-mo females but not in males. We also found that bone morphogenetic protein signaling through Smad1/5/9 was not altered by castration in atrophic muscle of 3-mo-old mice of both sexes. Moreover, castration decreased the sexual dimorphism regarding muscle performance. Together, these results demonstrated that in the long term, MGRF and FGRF promote muscle performance gain in mice during postnatal development, independently of muscle growth in males, largely via improving muscle contractile quality (force and power normalized), and that MGFR and FGRF also contribute to sexual dimorphism. However, the mechanisms underlying MGFR and FGRF actions remain to be determined.

scholarly journals SUN-253 PROKR2 Neurons of the Amygdalohippocampal Area in Reproductive Function

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Brenda Cisneros Larios ◽  
Carol F Elias
Keyword(s):  
Steroid Receptors ◽  
Reproductive Function ◽  
Sexually Dimorphic ◽  
Male Mice ◽  
Loss Of Function ◽  
Exposure Test ◽  
Male And Female ◽  
Female Mice ◽  
Reproductive Control

Abstract Kallmann Syndrome (KS) is characterized by infertility and anosmia due to deficiency in gonadotropin releasing hormone (GnRH) neuronal migration and olfactory bulb dysgenesis. Genetic studies have revealed that KS is caused by loss-of-function mutations in several genes including the prokineticin receptor 2 (PROKR2) gene (Abreu et al., 2008, Hardelin & Dode 2008). Mice with global deletion of Prokr2 replicate the phenotype of KS patients (Ng et al., 2005, Matsumoto et al., 2006). Whereas the role of PROKR2 during development is defined, little is known about PROKR2 neurons in adult reproduction. PROKR2 mRNA are highly expressed in reproductive control sites of the adult mouse brain (Cheng et al., 2006). Previous studies in our lab found PROKR2 mRNA and Prokr2-Cre GFP+ cells highly expressed in the amygdalohippocampal area (AHi, also called posterior nucleus of the amygdala) in a sexually-dimorphic pattern. Male mice have higher PROKR2 expression in the AHi compared to female mice (Mohsen et al., 2017). The amygdala is an important site of socio-sexual inputs and reproductive neuroendocrine responses in rodents and primates, including humans. We hypothesize Prokr2-Cre neurons in the AHi have a role in both male and female reproductive function. Using genetic tracing techniques, we mapped AHi Prokr2-Cre neuronal projections in both male and female mice and found dense innervation to reproductive control sites such as the medial preoptic area and the ventral premammillary nucleus in a sexually dimorphic pattern. A soiled bedding exposure test in sexually experienced male mice showed that an estimated 45% of cFos + cells in the AHi express Prokr2-Cre GFP. Dense sex steroid receptors expression was observed in AHi Prokr2-Cre GFP neurons of both male and female mice. Our preliminary data suggests AHi Prokr2-Cre neurons have a reproductive function in male and potentially also in female mice. Future studies will focus on selective activation and inhibition of these neurons using chemogenetic technology to determine putative inputs to brain sites that control the hypothalamo-pituitary-gonadal axis. We expect our studies will contribute to the understanding of the role of PROKR2 neurons in adult reproduction and reproductive deficits associated with PROKR2 mutations.

scholarly journals Bidirectional regulation of cognitive and anxiety-like behaviors by dentate gyrus mossy cells in male and female mice.

2021 ◽  
pp. JN-RM-1724-20
Author(s):  
Justin J Botterill ◽  
K Yaragudri Vinod ◽  
Kathleen J Gerencer ◽  
Cátia M Teixeira ◽  
John J LaFrancois ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Male And Female ◽  
Female Mice ◽  
Mossy Cells ◽  
Bidirectional Regulation

Dry leaf or twig mantis? A new genus and species of Acanthopidae with sexually dimorphic cryptic strategies (Insecta: Mantodea)

Zootaxa ◽  
2019 ◽  
Vol 4560 (2) ◽  
pp. 331 ◽  
Author(s):  
ANTONIO A. AGUDELO R. ◽  
CAROLINE MALDANER ◽  
JOSÉ A. RAFAEL
Keyword(s):  
Sexual Dimorphism ◽  
French Guiana ◽  
New Genus ◽  
Compound Eye ◽  
Brazilian Amazon ◽  
Sexually Dimorphic ◽  
New Genus And Species ◽  
Male And Female ◽  
Rich Diversity ◽  
The Many

Praying mantises (Mantodea) are distinct for their rich diversity of cryptic adaptations. Among the many strategies, dry-leaf mimicry have evolved multiple times in unrelated lineages from different zoogeographic regions, among them the Neotropical Acanthopidae. Here we describe Metacanthops fuscum n. gen. et n. sp. based on male and female specimens from the Brazilian Amazon. The recognition of this new acanthopid lineage revealed that Acanthops amazonica Beier, 1930 (currently assigned to Metilia Stål) is a member of Metacanthops and thus we transfer this species, now referable to as Metacanthops amazonica (Beier, 1930) n. comb., redescribe the holotype, and provide new data on its distribution in Brazil and French Guiana. Metacanthops is closely related to Metilia, from which its number of forefemoral posteroventral spines, head and compound eye shape, pronotal configuration, wings features, and the entirely brown habitus of males, can distinguish it. We highlight some aspects of sexual dimorphism in Metacanthops fuscum in relation to their dimorphic cryptic strategies, where males resemble a dry leaf and females a lichenous twig. We additionally establish five recently published names under genus Metilia as nomina nuda. 

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