1,721,025 research outputs found
Physiology and gene regulation of the brain NPY Y1 receptor
No full textNeuropeptide Y (NPY) is one of the most prominent and abundant neuropeptides in the mammalian brain where it interacts with a
family of G-protein coupled receptors, including the Y1 receptor subtype (Y1R). NPY-Y1R signalling plays a prominent role in the regulation
of several behavioural and physiological functions including feeding behaviour and energy balance, sexual hormone secretion,
stress response, emotional behaviour, neuronal excitability and ethanol drinking. Y1R expression is regulated by neuronal activity
and peripheral hormones. The Y1R gene has been isolated from rodents and humans and it contains multiple regulatory elements that
may participate in the regulation of its expression. Y1R expression in the hypothalamus is modulated by changes in energetic balance
induced by a wide variety of conditions (fasting, pregnancy, hyperglycaemic challenge, hypophagia, diet induced obesity). Estrogens
up-regulate responsiveness to NPY to stimulate preovulatory GnRH and gonadotropin surges by increasing Y1R gene expression both
in the hypothalamus and the pituitary. Y1R expression is modulated by different kinds of brain insults, such as stress and seizure activity,
and alteration in its expression may contribute to antidepressant action. Chronic modulation of GABAA receptor function by benzodiazepines
or neuroactive steroids also affects Y1R expression in the amygdala, suggesting that a functional interaction between the
GABAA receptor and Y1R mediated signalling may contribute to the regulation of emotional behaviour. In this paper, we review the
state of the art concerning Y1R function and gene expression, including our personal contribution to many of the subjects mentioned
above
Sex differences in behavioral and metabolic effects of gene inactivation: The neuropeptide Y and Y receptors in the brain
No full textBrain and gonadal hormones interplay controls metabolic and behavioral functions in a sex-related manner. However, most translational neuroscience research related to animal models of endocrine and psychiatric disorders are often carried out in male animals only. The Neuropeptide Y (NPY) system shows sex-dependent differences and is sensitive to gonadal steroids. Based on published data from our and other laboratories, in this review we will discuss the sex related differences of NPY action on energy balance, bone homeostasis and behavior in rodents with the genetic manipulation of genes encoding NPY and its Y1, Y2 and Y5 cognate receptors. Comparative analyses of the phenotype of transgenic and knockout NPY and Y receptor rodents unravels sex dependent differences in the functions of this neurotransmission system, potentially helping to develop therapeutics for a variety of sex-related disorders including metabolic syndrome, osteoporosis and ethanol addiction
Conditional inactivation of Npy1r gene in mice induces sex-related differences of metabolic and behavioral functions
No full textSex hormone-driven differences in gene expression have been identified in experimental animals, highlighting brain neuronal populations implicated in dimorphism of metabolic and behavioral functions. Neuropeptide Y-Y1 receptor (NPY-Y1R) system is sexually dimorphic and sensitive to gonadal steroids. In the present study we compared the phenotype of male and female conditional knockout mice (Npy1rrfb mice), carrying the inactivation of Npy1r gene in excitatory neurons of the brain limbic system. Compared to their male control (Npy1r2lox) littermates, male Npy1rrfb mice exhibited hyperactivation of the hypothalamic–pituitary–adrenal (HPA) axis that is associated with anxiety and executive dysfunction, reduced body weight growth, after-fasting refeeding, white adipose tissue (WAT) mass and plasma leptin levels. Conversely, female Npy1rrfb mice displayed an anxious-like behavior but no differences in HPA axis activity, executive function and body weight, compared to control females. Moreover, conditional inactivation of Npy1r gene induced an increase of subcutaneous and gonadal WAT weight and plasma leptin levels and a compensatory decrease of Agouti-related protein immunoreactivity in the hypothalamic arcuate (ARC) nucleus in females, compared to their respective control littermates. Interestingly, Npy1r mRNA expression was reduced in the ARC and in the paraventricular hypothalamic nuclei of female, but not male mice. These results demonstrated that female mice are resilient to hormonal and metabolic effects of limbic Npy1r gene inactivation, suggesting the existence of an estrogen-dependent relay necessary to ensure the maintenance of the homeostasis, that can be mediated by hypothalamic Y1R
Role of brain neuroactive steroids in the functional interplay between the GABA(A) and the NPY-Y-1 receptor mediated signals in the amygdala
No full textVarious lines of evidence suggest a functional interaction between GABA(A) and Neuropeptide Y (NPY)-Y-1 receptor (Y1R) mediated transmissions in various brain regions, which can be important in the regulation of sedation, feeding, anxious behaviour and neuronal excitability. By using a transgenic, mouse model carrying the murine Y1R gene promoter fused to the lacZ reporter gene (Y1R/LacZ mice), we showed that prolonged pharmacologically or physiologically induced changes in the cerebrocortical concentrations of the neuroactive steroids 3alpha-hydroxy5alpha-pregnan-20-one (3alpha,5alpha TH PROG) and tetrahydrodeoxycorticosterone (3alpha,5alpha TH DOC) increases Y1R/LacZ transgene expression in the central and medial amygdala, an effect similar to that induced by long-term treatment with positive modulators of the GABAA receptor complex (diazepam or abecarnil). We also demonstrated that fluctuations in the cerebrocortical concentrations of 3alpha, 5alpha-TH PROG and 3alpha,5alpha TH DOC during voluntary ethanol consumption and ethanol withdrawal induces a marked increase in Y1R gene expression that becomes apparent 48 h after withdrawal. These data provide evidence that neuroactive steroids may play an important role in the functional interaction between the GABA(A) receptor and NPY-Y1R mediated pathways in the amygdala, which might represent an important regulatory mechanism for modulation of several functions, including ethanol withdrawal. (c) 2006 Elsevier Inc. All rights reserved
Changes in expression of the neuropeptide YY1 receptor gene in the medial amygdala of transgenic mice during pregnancy and after delivery
No full textLong-term administration of progesterone or allopregnanolone was previously shown to increase Y-1 receptor gene expression in the medial amygdala of Y1R/LacZ transgenic mice, which harbor a construct comprising the murine Y-1 receptor gene promoter and a lacZ reporter. We have now investigated the effects of physiological fluctuations in the cerebrocortical concentrations of neuroactive steroids during pregnancy on Y1R/LacZ transgene expression by quantitative histochemical analysis of beta-galactosidase activity. Cerebrocortical concentrations of progesterone and its metabolites allopregnanolone and allotetrahydrodeoxycorticosterone were increased on day 18 of pregnancy and had returned to control values 2 days after delivery. Transgene expression in the medial amygdala was also increased on day 18 of pregnancy and had returned to control values 2 days after delivery. Similar results were obtained after analysis of Y1R mRNA levels in the medial amygdala of pregnant mice by in situ hybridization. Administration of the 5alpha-reductase inhibitor finasteride to pregnant mice prevented both the increase in the cerebrocortical concentrations of neuroactive steroids as well as the increase in transgene expression. These data suggest that fluctuations in the brain concentrations of endogenous neuroactive steroids during pregnancy are associated with changes in Y-1 receptor gene expression in the medial amygdala, further supporting a functional interaction between the GABAergic and NPY-Y-1 receptor systems
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Neuroanatomical and pharmacological evidence for a functional interaction between GABAergic and NPY-Y1 transmission in the amygdala of Y1R/LacZ transgenic mice
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