The Role of Interleukin-10 in Mediating the Effect of Immune Challenge on Mouse Gonadotropin-Releasing Hormone Neurons In Vivo

Klaudia Barabás, Zsuzsanna Barad, Ádám Dénes, Janardhan P. Bhattarai, Seong Kyu Han, Endre Kiss, G. Sármay, István M. Ábrahám

Research output: Contribution to journalArticle

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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.

Original languageEnglish
JournaleNeuro
Volume5
Issue number5
DOIs
Publication statusPublished - Sep 1 2018

Fingerprint

Gonadotropin-Releasing Hormone
Interleukin-10
Neurons
T-Lymphocytes
Phosphorylation
Cytokines
Estrous Cycle
Knockout Mice
Fluorescein-5-isothiocyanate
Brain
Hypothalamus
Fertility
B-Lymphocytes
Anti-Inflammatory Agents
Immunohistochemistry
Maintenance
Lymphocytes
Inflammation
fluorescein isothiocyanate-keyhole limpet hemocyanin
Therapeutics

Keywords

  • ERK1/2
  • GnRH neurons
  • IL-10
  • immune challenge
  • T-cell-dependent B-cell response

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Barabás, K., Barad, Z., Dénes, Á., Bhattarai, J. P., Han, S. K., Kiss, E., ... Ábrahám, I. M. (2018). The Role of Interleukin-10 in Mediating the Effect of Immune Challenge on Mouse Gonadotropin-Releasing Hormone Neurons In Vivo. eNeuro, 5(5). https://doi.org/10.1523/ENEURO.0211-18.2018

The Role of Interleukin-10 in Mediating the Effect of Immune Challenge on Mouse Gonadotropin-Releasing Hormone Neurons In Vivo. / Barabás, Klaudia; Barad, Zsuzsanna; Dénes, Ádám; Bhattarai, Janardhan P.; Han, Seong Kyu; Kiss, Endre; Sármay, G.; Ábrahám, István M.

In: eNeuro, Vol. 5, No. 5, 01.09.2018.

Research output: Contribution to journalArticle

Barabás, Klaudia ; Barad, Zsuzsanna ; Dénes, Ádám ; Bhattarai, Janardhan P. ; Han, Seong Kyu ; Kiss, Endre ; Sármay, G. ; Ábrahám, István M. / The Role of Interleukin-10 in Mediating the Effect of Immune Challenge on Mouse Gonadotropin-Releasing Hormone Neurons In Vivo. In: eNeuro. 2018 ; Vol. 5, No. 5.
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