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Groei En Ontwikkeling Bonobo's Zijn (ook) bij bonobo’s de mannen het zwakke geslacht? Jeroen Stevens & Verena Behringer Wetenschappelijk Symposium Nederlandse Vereniging van Dierentuinen 30 Mei 2018, Apeldoorn 1 Zijn (ook) bij bonobo’s de mannen het zwakke geslacht? Een spannend verhaal in sneltreinvaart over vreemde piramides, over zombiecellen, en over Griekse schikgodinnen (maar niet over “dat chimpansees in dierentuinen een lagere immuunrespons vertonen dan in het wild” want daar heb ik vandaag geen tijd voor) 2 Inleiding: Project groei & ontwikkeling 3 Inleiding: Project groei & ontwikkeling Voortplanting Groei onderhoud 1. Begin van 2. Groei vd 3. Gezond voortplanting voorarm ouder worden Inleiding: Project groei & ontwikkeling Inleiding Gegevens hormoonanalyse Waar zijn de oude mannen naartoe?? Behringer et al. submitted Inleiding Levensverwachting - Chimpansees Mannen in het wild en in dierentuinen hebben: - Een kortere levensverwachting - Een lagere kans op overleving Dyke et al., 1995; Schubert et al., 2013; Muller and Wrangham, 2014 1.0 0.8 0.6 Rate 0.4 0.2 Survivorship 0.0 10 20 30 40 50 Life Span (years) Modified after Schubert et al. 2013 Inleiding Levensverwachting – Bonobo’s - Enkel gegevens uit dierentuinen - Vrouwen hebben langere levensverwachting dan mannen Schubert et al., 2013 1.0 0.8 0.6 Rate 0.4 0.2 Survivorship 0.0 10 20 30 40 50 Life Span (years) Modified after Schubert et al. 2013 Inleiding Leefdtijdspiramiden in dierentuinpopulaties Pan troglodytes verus EEP Pan paniscus EEP & SSP Hoe komt het dat zo weinig oudere bonobomannen zijn? Deel 1: Stress - Cortisol Deel 2: Gezond ouder worden - IGFBP-3 - Klotho © Jeroen Stevens Deel 3: Immuunrespons - Testosteron 1) Stress Glucocorticoiden (GCs) regelen de stress respons - Bv cortisol Stressor - GCs verhogen in reactie op de stressor 1) Stress Wat doet cortisol? 1) Geeft energie vrij verhoging bloedsuiker 2) Onderdrukt het immuun systeem Is er een geslachtsverschil in cortisol? Flinn 2008 1) Stress Cortisol in speeksel 50 Gorilla’s & orang oetans: 20 Geen geslachtsverschil 10 Chimpansees: 5 Meer cortisol bij vrouwen 2 dan bij mannen 1 Salivary cortisol (ng/ml) cortisol Salivary Bonobo’s: 0.5 Meer cortisol bij mannen dan bij vrouwen f m f m f m f m Gorilla Orangutan Chimpanzee Bonobo DUS: Bonobo mannen hebben meer stress dan vrouwen ~ effect op de immuniteit (?) Modified after Behringer et al. 2013 2) Gezond ouder worden De meeste cellen in het lichaam voeren geprogrammeerde cel dood uit wanneer ze worden beschadigd Science in a nutshell: youtube.com/watch?v=MjdpR-TY6QU 2) Gezond ouder worden Maar sommige cellen, zoals „senescentiecellen“ voeren geen geprogrammeerde celdood uit „Zombie cellen“ Science in a nutshell: youtube.com/watch?v=MjdpR-TY6QU 2) Gezond ouder worden Hoe ouder je wordt, hoe meer Zombie cellen zich opstapelen in je lichaam Science in a nutshell: youtube.com/watch?v=MjdpR-TY6QU 2) Gezond ouder worden „Zombiecellen“ beschadigen de omliggende weefsels - Worden geassocieerd met veel (ouderdoms)ziektes - IGFBP-3 reguleert geprogrammeerde celdood & onderhoudt gezonde cellen Science in a nutshell: youtube.com/watch?v=MjdpR-TY6QU 2) Gezond ouder worden IGFBP-3 & ouder worden bij mensen Infant 3 - Child Adolescent IGFBP Adult Old adult Collett-Solberg and Cohen 2000 , Baxter et al., 2010 2) Gezond ouder worden - Mensen: vrouwen hogere IGBPF-3 dan mannen Jansen et al. (1998) Men Women /ml) ng 3 ( - IGFBP Age classes (years) After Probst-Hensch et al. 2003 2) Urinary IGFBP-3 (ng/ml corr. SG) Gezond ouder Age Age ( worden years ) IGFBP - 3 in 3 Urinary IGFBP-3 (ng/ml corr. SG) urine Age Age ( years Behringer et2016 al. Behringer ) 2) Gezond ouder worden IGFBP-3 in urine . SG] corr /ml ng [ level 3 - IGFBP Urinary Age (years) Behringer et al. 2016 2) Gezond ouder worden Klotho en deKlotho draad des levens 2) Gezond ouder worden Klotho en de draad des levens • Klotho gen bij muizen – Mutante muizen waarbij klotho niet tot expressie komt, ontwikkelen verschillende aandoeningen die lijken menselijke verouderingsproces – Ook bij mensen en rhesusapen 2) Gezond ouder worden Alpha klotho in bloed Decline in alpha kotho levels with age Behringer et al. In prep 2) Gezond ouder worden Alpha klotho in bloed Behringer et al. In prep 3) Immuunrespons Testosteron als immuno-suppressor - Verhoogd testosteron = toename van energie in de spieren (competitie tussen mannen) - Testosteron heeft ook een rol als immuno suppressor Immune kenmerk Testosteron onderdrukt system Hamilton & Zuk, 1992; Folstad & Karter, 1992; Roberts et al. 2004 3) Immuunrespons Testosteron in serum Behringer et al. In prep Besluit Zijn er geslachtsverschillen in stress? - Bonobo’s: mannen hebben hogere cortisol niveau - Chimpansees: vrouwen hebben hogere cortisol Zijn er geslachtsverschillen in gezond ouder worden? - Bonobo’s: vrouwtjes zijn beter gewapend tegen effecten van ouder worden - Chimpansees: geen duidelijke geslachtsverschillen Zijn er geslachtsverschillen in testosteron? - Beide soorten : mannetjes hogere testosteron Besluit • Voor bonobo’s lijkt de kortere levensduur van mannetjes te kunnen worden verklaard door de bevindingen uit het hormoon onderzoek. – lagere cortisol, lagere klotho, hogere IGFBP3, lagere testosteron • Voor chimpansees lijkt het verhaal complexer, misschien spelen hier externe factoren een grotere rol – bv minder competitie bij chimpanseemannen in dierentuinen. Besluit • Ze leefden misschien niet lang en gelukkig… • Maar samenwerking tussen onderzoeks- instellingen en dierentuinen geven inzichten die nuttig zijn voor fundamenteel begrip van mensapen, maar ook praktische implicaties kunnen hebben voor welzijn Dankwoord The work reported herein would not have been possible without the help of the care takers, curators, veterinarians and directors of the zoos contributing data, hosting the project and providing vital information. I would like to express my sincere thanks and gratitude to the staff of Aalborg Zoo, Allwetterzoo Münster, Artis, Apenheul, Badoca Safari Park, Belfast Zoo, Bergzoo Halle, Bioparc Fuengirola, Bioparc Valencia, Boras Djurpark, Burgers’ Zoo, Columbus Zoo and Aquarium, Copenhagen Zoo, Dudley Zoological Gardens, Furuviksparken, Givskud Zoo, Kittenberger Kalman Zoo & Botanical Garden, Kristiansand Dyrepark, La Vallée des Singes, Ljubljana Zoo, Milwaukee County Zoo, Ogrod Zoologiczny w Warszawie, Tierpark Hellabrunn, Parco Natura Viva, Planckendael Wild Animal Park, San Diego Wild Animal Park, San Diego Zoo, Tisch Family Zoological Gardens, Twycross Zoo, Walter Zoo, Wilhelma, Zoo Antwerpen, Zoo am Meer, Zoo Augsburg, Zoo Aquarium de la Casa de Campo de Madrid, Zoo Berlin, Zoo Cologne, Zoo Frankfurt, Zoo Gdansk, Zoo Heidelberg, Zoo Magdeburg, Zoo Leipzig, Zoologicka Zahrada Bratislava, ZOOM Erlebniswelt Gelsenkirchen and Zoo Wuppertal. Conclusion Where are all the old male chimpanzees gone? Wild adult males: Zoo adult males: - Aggressive interaction, - Little risk taking behaviors physical aggression - Boarder patrols, lethal intergroup encounters Physiological challenges: Primary causes of mortality - No clear sex differences are infection diseases. Females: - Higher cortisol Neither differences in external - Lower klotho factors nor in internal factors - Higher IGFBP-3 alone explains the sex - Lower testosterone differences in life expectancy. Conclusion Where are all the old male bonobos gone? Wild adult males: Zoo adult males: - Less aggressive - Most of the behaviours are interaction, rarely physical absent or rare aggression - No boarder patrols or lethal intergroup encounters Male bonobos are less good prepared for physiological Physiological challenges: challenges, but some of them - Females are better face more challenges than prepared females do. - Lower cortisol - Lower klotho Maybe males are more - Higher IGFBP-3 vulnerable to stress and - Lower testosterone diseases. Introduction- Immune response Testosterone differences in males between species? ) Males Males 180 100 60 100 Relative testosterone amount Relative 20 20 Urinary testosterone metabolite (ng/mg CR (ng/mg metabolite testosterone Urinary Bonobo Chimpanzee Bonobo Chimpanzee Human Gorillas Orangutans After Hagey & Czekala 2003 After Sannen et al. 2003 No species difference Species difference Introduction - Neopterin Responses of the immune system to infection NON-SPECIFIC IMMUNITY = Innate immunity - Response to pathogens in a general way - No long-lasting or protective immunity to Neopterin the host Results - Neopterin Urinary neopterin is increased during infections Overlap: Sick vs. healthy Behringer et al. 2017 Results - Neopterin Urinary neopterin levels in „healthy“ chimpanzees © Anna Preis Behringer et al. In prep Introduction- Immune response Testosterone differences between sexes? 180 ** /L] pmol 100 [ * 20 testosterone Urinary testosterone metabolite (ng/mg CR) (ng/mg metabolite testosterone Urinary Female Male Female Male Bonobo Chimpanzee After Sannen et al. 2003 Salivary Sex difference Bonobos: Small After Wobber et al. 2013 Chimpanzees: Large No sex difference in bonobos Introduction - Neopterin T-cells are immune cells that are part of specific and non-specific immune responses T-CELLS: - Different types of T-cells - Focus on T-helper (Th) cells Cell-mediated Immunity Th1 INF-γ IL-12 Macrophage Antigen activation recognition Th IL-4 Humoral Immunity Th2 IL-4 Macrophage deactivation Introduction - Neopterin Neopterin is released by activated macrophages Cell-mediated Immunity Macrophage activation Antigen IL-12 recognition Th Th1 INF-γ Reactive oxygen species Neopterin Murr et al. 2002 Results - Neopterin Urinary neopterin is increased during infections Urinary neopterin (µmol/molcrea) levels during the study period. Samples from the respiratory outbreak are highlighted in red. Wu et al. In prep Introduction Where have all the old men gone? - Does male physiology differ from female physiology? - Is one sex better prepared for physiological challenges? Does the zoo environment has an effect on immune system response?.
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