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      The Impact of Exposure to a Novel Female on Symptoms of Infection and on the Reproductive Axis

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          Abstract

          Background/Aim: Sickness behaviors are the behavioral alterations animals exhibit during the course of an infection, often accompanied by reduced reproductive activity. Adopting sickness behaviors may aid in overcoming the infection, by diverting energy from routine activities towards enhancement of the immune system. Nonetheless, sickness behaviors are plastic, being influenced by specific environmental and social circumstances. Here, we tested whether the presentation of a novel female to males suffering from a simulated infection could impact the behavioral effects of sickness, the reproductive axis, or both. Methods: Male zebra finches were housed in isolation and injected intramuscularly with lipopolysaccharide or saline. Behaviors were recorded before (3 h before injection) and after (3.5 h after injection) addition of a novel female to the cage for 30 min. Four hours after injection, we collected the brain and testis for the analysis of important reproductive axis modulators, gonadotropin-releasing hormone, and gonadotropin-inhibitory hormone, and to quantify gene expression of a proinflammatory cytokine involved in the regulation of sickness behaviors [interleukin (IL)-1β]. Testosterone was quantified in the plasma. Results: The presence of a novel female diminished sickness behaviors and induced alterations in the reproductive axis within 30 min, with no associated changes in brain gene expression of IL-1β. Social environment itself altered brain gene expression of IL-1β. Conclusions: Male zebra finches prioritize the opportunity to mate versus investment in recovery from an infection, as determined by reduced expression of sickness behaviors when a potential mate was present. The behavioral effects of IL-1β appear to be context dependent in this species.

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          Most cited references48

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          Comprehensive algorithm for quantitative real-time polymerase chain reaction.

          Quantitative real-time polymerase chain reactions (qRT-PCR) have become the method of choice for rapid, sensitive, quantitative comparison of RNA transcript abundance. Useful data from this method depend on fitting data to theoretical curves that allow computation of mRNA levels. Calculating accurate mRNA levels requires important parameters such as reaction efficiency and the fractional cycle number at threshold (CT) to be used; however, many algorithms currently in use estimate these important parameters. Here we describe an objective method for quantifying qRT-PCR results using calculations based on the kinetics of individual PCR reactions without the need of the standard curve, independent of any assumptions or subjective judgments which allow direct calculation of efficiency and CT. We use a four-parameter logistic model to fit the raw fluorescence data as a function of PCR cycles to identify the exponential phase of the reaction. Next, we use a three-parameter simple exponent model to fit the exponential phase using an iterative nonlinear regression algorithm. Within the exponential portion of the curve, our technique automatically identifies candidate regression values using the P-value of regression and then uses a weighted average to compute a final efficiency for quantification. For CT determination, we chose the first positive second derivative maximum from the logistic model. This algorithm provides an objective and noise-resistant method for quantification of qRT-PCR results that is independent of the specific equipment used to perform PCR reactions.
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            Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity.

            Sickness refers to a coordinated set of subjective, behavioural and physiological changes that develop in sick individuals during the course of an infection. These changes are due to the effects of interleukin-1 (IL-1) and other proinflammatory cytokines on brain cellular targets. Sickness behaviour is mediated by proinflammatory cytokines that are temporarily expressed in the brain during infection. These centrally produced cytokines are the same as those expressed by innate immune cells and they act on brain receptors that are identical to those characterized on immune cells. Primary afferent nerves represent the main communication pathway between peripheral and central cytokines. Proinflammatory cytokines modulate learning and memory processes. The expression and action of proinflammatory cytokines in the brain in response to peripheral cytokines are regulated by various molecular intermediates including anti-inflammatory cytokines such as interleukin-10 (IL-10) and the IL-1 receptor antagonist (IL-1ra), growth factors such as insulin-like growth factor-1 (IGF-1), hormones such as glucocorticoids and neuropeptides such as vasopressin and alpha-melanotropin.
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              Avoiding the ‘Costs’ of Testosterone: Ecological Bases of Hormone-Behavior Interactions

              A combination of laboratory and field investigations of birds has shown that expression of behavior such as territorial aggression can occur throughout the year in many species and in different life history stages. Although it is well known that testosterone regulates territorial aggression in males during the breeding season, the correlation of plasma testosterone and aggression appears to be limited to periods of social instability when a male is challenged for his territory by another male, or when mate-guarding a sexually receptive female. How essentially identical aggression is modulated in non-breeding life history stages is not fully resolved, but despite low circulating levels of testosterone outside the breeding season, expression of territorial aggression does appear to be dependent upon aromatization of testosterone and an estrogen receptor-mediated mechanism. There is accumulating evidence that prolonged high levels of circulating testosterone may incur costs that may potentially reduce lifetime fitness. These include interference with paternal care, exposure to predators, increased risk of injury, loss of fat stores and possibly impaired immune system function and oncogenic effects. We propose six hypotheses to explain how these costs of high testosterone levels in blood may be avoided. These hypotheses are testable and may reveal many mechanisms resulting from selection to avoid the costs of testosterone. It should also be noted that the hypotheses are applicable to vertebrates in general, and may also be relevant for other hormones that have a highly specialized suite of actions in one life history stage (such as breeding), but also have a limited action in other life history stages when the full spectrum of effects would be inappropriate.
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                1021-7401
                1423-0216
                2013
                September 2013
                05 September 2013
                : 20
                : 6
                : 348-360
                Affiliations
                aDepartment of Integrative Biology and bHelen Wills Neuroscience Institute, University of California, Berkeley, Calif., and cDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Calif., USA; dPrograma Graduado em Areas da Biologia Basica e Aplicada, University of Porto, Porto, Portugal
                Author notes
                *Patricia Castro Lopes, Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich (Switzerland), E-Mail patricia.lopes@ieu.uzh.ch
                Article
                353779 Neuroimmunomodulation 2013;20:348-360
                10.1159/000353779
                24008626
                a219e68a-a9bf-42d9-987c-2b0dd6196761
                © 2013 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 17 April 2013
                : 13 June 2013
                Page count
                Figures: 4, Pages: 13
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Testicular response,Social interactions,Sickness behavior, Interleukin-1,Testosterone,Hypothalamic-pituitary-gonadal axis,Gonadotropin-inhibitory hormone,Gonadotropin-releasing hormone

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