Barabás, Klaudia and Barad, Zsuzsanna and Dénes, Ádám and Bhattarai, Janardhan P and Han, Seong-Kyu and Kiss, Endre and Sármay, Gabriella and Ábrahám, István (2018) The Role of Interleukin-10 in Mediating the Effect of Immune Challenge on Mouse Gonadotropin-Releasing Hormone Neurons In Vivo. ENEURO, 5 (5). No. e0211. ISSN 2373-2822
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Abstract
Immune challenge alters neural functioning via cytokine production. Inflammation has profound impact on the central regulation of fertility, but the mechanisms involved are not clearly defined. The anti-inflammatory cytokine interleukin (IL)-10 is responsible for balancing the immune response in the brain. To examine whether IL-10 has an effect on the function of the gonadotropin-releasing hormone (GnRH) neurons, we first examined the effect of immune responses with distinct cytokine profiles, such as the T cell-dependent (TD) and T cell-independent (TI) B-cell response. We investigated the effect of the TD and TI immune responses on ERK1/2 phosphorylation in GnRH neurons by administering fluorescein isothiocyanate/keyhole limpet hemocyanin (KLH-FITC) or dextran-FITC to female mice. Although dextran-FITC had no effect, KLH-FITC induced ERK1/2 phosphorylation in GnRH neurons after 6 d. KLH-FITC treatment increased the levels of IL-10 in the hypothalamus (HYP), but this treatment did not cause lymphocyte infiltration or an increase in the levels of proinflammatory cytokines. In IL-10 knock-out (KO) mice, KLH-FITC-induced ERK1/2 phosphorylation in the GnRH neurons was absent. We also showed that in IL-10 KO mice, the estrous cycle was disrupted. Perforated patch-clamp recordings from GnRH-GFP neurons, IL-10 immunohistochemistry, and in vitro experiments on acute brain slices revealed that IL-10 can directly alter GnRH neuron firing and induce ERK1/2 phosphorylation. These observations demonstrate that IL-10 plays a role in influencing signaling of GnRH neurons in the TD immune response. These results also provide the first evidence that IL-10 can directly alter the function of GnRH neurons and may help the maintenance of the integrity of the estrous cycle.
| Item Type: | Article |
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| Additional Information: | Funding Agency and Grant Number: Hungarian Brain Research Program [KTIA_NAP_13-2014-0001, 20017-1.2.1-NKP -2017-00002]; National Science FundationNational Science Foundation (NSF) [112807]; Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs [EFOP-3.6.2-16-2017-00008]; "The role of neuro-inflammation in neurodegeneration: from molecules to clinics" Ministry of Human Capacities [EFOP-3.6.2-16-2017-00008, GINOP-2.3.2-15-2016-00048]; Otago School of Medical Sciences, Department of Physiology, University of Otago Funding text: This work was supported by the Hungarian Brain Research Program (KTIA_NAP_13-2014-0001, 20017-1.2.1-NKP -2017-00002); National Science Fundation (112807); the Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs (EFOP-3.6.1.-16-2016-00004); "The role of neuro-inflammation in neurodegeneration: from molecules to clinics" Ministry of Human Capacities; (EFOP-3.6.2-16-2017-00008), GINOP-2.3.2-15-2016-00048, Stay Alive; and the Otago School of Medical Sciences, Department of Physiology, University of Otago. |
| Uncontrolled Keywords: | IL-10; ERK1/2; GNRH NEURONS; T-cell-dependent B-cell response; immune challenge |
| Subjects: | R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 13 Dec 2024 12:21 |
| Last Modified: | 13 Dec 2024 12:21 |
| URI: | https://real.mtak.hu/id/eprint/211627 |
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