Immunohistochemical evidence for the relationship between microglia and GnRH neurons in the preoptic area of ovariectomized rats with and without steroid replacement

Fujioka, Hikaru; Kakehashi, Chiaki; Funabashi, Toshiya; Akema, Tatsuo

doi:10.1507/endocrj.ej12-0280

Cited by 16 publications

(12 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, activated microglia can secrete IL-10 (Park et al, 2007; Lim et al, 2013; Lobo-Silva et al, 2016). Furthermore, Fujioka et al (2013) revealed evidence for a close relationship between microglia and GnRH neurons, providing a functional platform for microglia-derived IL-10 activity on GnRH neurons. Based on these findings, we have speculated that IL-10 produced by microglia might alter the functions of GnRH neurons.…”

Section: Discussionmentioning

confidence: 96%

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

Barabás

Barad

Bhattarai

et al. 2018

eNeuro

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 96%

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

Barabás

Barad

Bhattarai

et al. 2018

eNeuro

View full text Add to dashboard Cite

show abstract

“…The first paper is a qualitative study observing microglia in association with GnRH neuron soma of adult female rats. 23 The second paper is our recent study highlighting that, in addition to the presence of microglia in the vicinity of GnRH neurons, their filopodia ensheath GnRH neurons during postnatal development. 22 Concerning oligodendrocytes, the recently published study by Pellegrino et al 24 They are also the most extensively studied for their role in regulating GnRH neuron activity, secretion and reproductive outcomes.…”

Section: Glial Cells Within the Brainmentioning

confidence: 99%

Unusual suspects: Glial cells in fertility regulation and their suspected role in polycystic ovary syndrome

Desroziers

2022

J Neuroendocrinology

View full text Add to dashboard Cite

Gonadotropin-releasing-hormone (GnRH) neurons sitting within the hypothalamus control the production of gametes and sex steroids by the gonads, therefore ensuring survival of species. As orchestrators of reproductive function, GnRH neurons integrate information from external and internal cues. This occurs through an extensively studied neuronal network known as the "GnRH neuronal network." However, the brain is not simply composed of neurons. Evidence suggests a role for glial cells in controlling GnRH neuron activity, secretion and fertility outcomes, although numerous questions remain. Glial cells have historically been seen as support cells for neurons. This idea has been challenged by the discovery that some neurological diseases originate from glial dysfunction. The prevalence of infertility disorders is increasing worldwide, with one in four couples being affected; therefore, it remains essential to understand the mechanisms by which the brain controls fertility. The "GnRH glial network" could be a major player in infertility disorders and represent a potential therapeutic target. In polycystic ovary syndrome (PCOS), the most common infertility disorder of reproductive aged women worldwide, the brain is considered a prime suspect. Recent studies have demonstrated pathological neuronal wiring of the "GnRH neuronal network" in PCOS-like animal models. However, the role of the "GnRH glial network" remains to be elucidated. In this review, I aim to propose glial cells as unusual suspects in infertility disorders such as PCOS. In the first part, I state our current knowledge about the role of glia in the regulation of GnRH neurons and fertility.In the second part, based on our recent findings, I discuss how glial cells could be implicated in PCOS pathology.

show abstract

“…Interestingly, fatty acids, and not obesity per se, are required to induce hypothalamic microglial activation, since genetically obese mice do not present hypothalamic microglia activation in the absence of high-fat diet [ 16 , 42 ]. There exists evidence of intercellular communication, mediated by prostaglandins, from microglia to GnRH cells [ 43 ]. Prostaglandins seem to be an important mediator.…”

Section: Potential Mechanisms Of Diet-induced Precocious Pubarchementioning

confidence: 99%

Diet-Induced Hypothalamic Inflammation, Phoenixin, and Subsequent Precocious Puberty

et al. 2021

View full text Add to dashboard Cite

Recent studies have shown a rise in precocious puberty, especially in girls. At the same time, childhood obesity due to overnutrition and energy imbalance is rising too. Nutrition and fertility are currently facing major challenges in our societies, and are interconnected. Studies have shown that high-fat and/or high-glycaemic-index diet can cause hypothalamic inflammation and microglial activation. Molecular and animal studies reveal that microglial activation seems to produce and activate prostaglandins, neurotrophic factors activating GnRH (gonadotropin-releasing hormone expressing neurons), thus initiating precocious puberty. GnRH neurons’ mechanisms of excitability are not well understood. In this review, we study the phenomenon of the rise of precocious puberty, we examine the physiology of GnRH neurons, and we review the recent literature regarding the pathophysiological mechanisms that connect diet-induced hypothalamic inflammation and diet-induced phoenixin regulation with precocious puberty.

show abstract

Immunohistochemical evidence for the relationship between microglia and GnRH neurons in the preoptic area of ovariectomized rats with and without steroid replacement

Cited by 16 publications

References 33 publications

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

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

Unusual suspects: Glial cells in fertility regulation and their suspected role in polycystic ovary syndrome

Diet-Induced Hypothalamic Inflammation, Phoenixin, and Subsequent Precocious Puberty

Contact Info

Product

Resources

About