Interleukin-1 Inhibits NMDA-Stimulated GnRH Secretion: Associated Effects on the Release of Hypothalamic Inhibitory Amino Acid Neurotransmitters

Feleder, Carlos; Arias, Pablo; Refojo, Damián; Nacht, Silvina; Moguilevsky, Jaime A.

doi:10.1159/000026419

Cited by 22 publications

(7 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-1 potentiates GABA signalling through multiple mechanisms: it recruits GABA A receptors to the cell surface76; it increases Cl − uptake by acting on GABA A receptors77; and it induces a delayed potentiation of the GABA-elicited Cl − current, an effect that is suppressed by the IL-1 receptor antagonist76. The observation that IL-1 potentiates the effects of GABA in the DRN is in agreement with data which demonstrate that IL-1 enhances GABA-induced hyperpolarization and inhibition in other brain regions where IL-1 acts both pre- and postsynaptically: IL-1 increases GABA release in anterior hypothalamic/pre-optic area slice preparations78 and in brain explants79 and enhances GABAergic inhibitory postsynaptic potentials in hippocampal neurons80,81.…”

Section: Interactions Between Il-1 and 5-htsupporting

confidence: 88%

How (and why) the immune system makes us sleep

2009

View full text Add to dashboard Cite

Good sleep is necessary for physical and mental health. For example, sleep loss impairs immune function, and sleep is altered during infection. Immune signalling molecules are present in the healthy brain, where they interact with neurochemical systems to contribute to the regulation of normal sleep. Animal studies have shown that interactions between immune signalling molecules (such as the cytokine interleukin 1) and brain neurochemical systems (such as the serotonin system) are amplified during infection, indicating that these interactions might underlie the changes in sleep that occur during infection. Why should the immune system cause us to sleep differently when we are sick? We propose that the alterations in sleep architecture during infection are exquisitely tailored to support the generation of fever, which in turn imparts survival value.Modern sleep research began in 1953, with the discovery of rapid eye movement (REM) sleep and the realization that sleep is an active process that consists of two distinct phases. More than half a century of intense investigation has yet to provide an unequivocal answer to the question, 'Why do we sleep?' Nonetheless, we are beginning to understand the contribution of sleep to fundamental brain processes 1,2 .In contrast to our lack of knowledge regarding the precise functions of sleep, we do know why we have an immune system. Living organisms are subject to constant attack by various pathogens, and the complex networks of physical and biochemical components that constitute the immune system keep the organism alive. Like sleep research, the field of immunology is a relatively young discipline. It should therefore not come as a surprise that systematic investigations of interactions between sleep and the immune system have only been conducted in the past 25 years (TIMELINE). NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAlthough we briefly touch on the general role of sleep in health and disease, in this Review we focus on those areas of research that are most relevant to sleep as a component of the host defence against microbial pathogens. Links between the CNS and the peripheral immune system are now well established, and much is known about the mechanisms by which bidirectional communication occurs between these systems 3 . As a result of neuro-immune interactions, sleep loss alters immune function and immune challenges alter sleep. Thus, chronic sleep loss results in pathologies that are associated with increases in inflammatory mediators, and inflammatory mediators that are released during immune responses to infection alter CNS processes and behaviour, including sleep.One class of immunomodulators, cytokines, has been extensively studied both with respect to host responses to infection and as regulators of physiological sleep. In this Review, we briefly summarize what is known about cytokines in the brain as regulators of normal, physiological sleep and what is known about their role in mediating the changes in sleep that are in...

show abstract

Section: Interactions Between Il-1 and 5-htsupporting

confidence: 88%

How (and why) the immune system makes us sleep

2009

View full text Add to dashboard Cite

show abstract

“…Earlier studies demonstrated inhibitory eVects of IL-1 on the hippocampal long-term potentiation (LTP) [67]. The exact mechanisms of the inhibitory eVects of IL-1 on synaptic plasticity are not completely elucidated; however, in vitro studies performed on pharmacologically isolated NMDA receptors revealed that administration of IL-1 was associated with signiWcant decrease in NMDA receptor excitatory post-synaptic potentials [14,41]. Similar eVects with regard to LTP were observed in the transgenic mouse model over-expressing IL-6.…”

Section: Cytokines and Brain Plasticitymentioning

confidence: 99%

Inflammation, plasticity and real-time imaging after cerebral ischemia

2009

View full text Add to dashboard Cite

With an incidence of approximately 350 in 100,000, stroke is the third leading cause of death and a major cause of disability in industrialized countries. At present, although progress has been made in understanding the molecular pathways that lead to ischemic cell death, the current clinical treatments remain poorly eVective. There is mounting evidence that inXammation plays an important role in cerebral ischemia. Experimentally and clinically, brain response to ischemic injury is associated with an acute and prolonged inXammatory process characterized by the activation of resident glial cells, production of inXammatory cytokines as well as leukocyte and monocyte inWltration in the brain, events that may contribute to ischemic brain injury and aVect brain recovery and plasticity. However, whether the post-ischemic inXammatory response is deleterious or beneWcial to brain recovery is presently a matter of debate and controversies. Here, we summarize the current knowledge on the molecular mechanisms underlying post-ischemic neuronal plasticity and the potential role of inXammation in regenerative processes and functional recovery after stroke. Furthermore, because of the dynamic nature of the brain inXammatory response, we highlight the importance of the development of novel experimental approaches such as real-time imaging. Finally, we discuss the novel transgenic reporter mice models that have allowed us to visualize and to analyze the processes such as neuroinXammation and neuronal repair from the ischemic brains of live animals.

show abstract

“…IL‐1 enhances GABA inhibitory effects acting at both pre‐ and post‐synaptic levels. IL‐1 enhances GABA release (Feleder et al ., 2000; Tabarean et al ., 2006) and it also enhances GABA‐induced post‐synaptic responses in different in vivo and in vitro experimental models (Miller et al ., 1991; Luk et al ., 1999; Serantes et al ., 2006). The present study was designed to test the hypothesis that IL‐1 inhibits DRN serotonergic neurons by potentiating GABAergic inhibition.…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐1 inhibits firing of serotonergic neurons in the dorsal raphe nucleus and enhances GABAergic inhibitory post‐synaptic potentials

Brambilla

Franciosi

Opp

et al. 2007

Eur J of Neuroscience

View full text Add to dashboard Cite

In vitro electrophysiological data suggest that interleukin-1 may promote non-rapid eye movement sleep by inhibiting spontaneous firing of wake-active serotonergic neurons in the dorsal raphe nucleus (DRN). Interleukin-1 enhances GABA inhibitory effects. DRN neurons are under an inhibitory GABAergic control. This study aimed to test the hypothesis that interleukin-1 inhibits DRN serotonergic neurons by potentiating GABAergic inhibitory effects. In vitro intracellular recordings were performed to assess the responses of physiologically and pharmacologically identified DRN serotonergic neurons to rat recombinant interleukin-1beta. Coronal slices containing DRN were obtained from male Sprague-Dawley rats. The impact of interleukin-1 on firing rate and on evoked post-synaptic potentials was determined. Evoked post-synaptic potentials were induced by stimulation with a bipolar electrode placed on the surface of the slice ventrolateral to DRN. Addition of interleukin-1 (25 ng/mL) to the bath perfusate significantly decreased firing rates of DRN serotonergic neurons from 1.3 +/- 0.2 Hz (before administration) to 0.7 +/- 0.2 Hz. Electrical stimulation induced depolarizing evoked post-synaptic potentials in DRN serotonergic neurons. The application of glutamatergic and GABAergic antagonists unmasked two different post-synaptic potential components: a GABAergic evoked inhibitory post-synaptic potentials and a glutamatergic evoked excitatory post-synaptic potentials, respectively. Interleukin-1 increased GABAergic evoked inhibitory post-synaptic potentials amplitudes by 30.3 +/- 3.8% (n = 6) without affecting glutamatergic evoked excitatory post-synaptic potentials. These results support the hypothesis that interleukin-1 inhibitory effects on DRN serotonergic neurons are mediated by an interleukin-1-induced potentiation of evoked GABAergic inhibitory responses.

show abstract

Interleukin-1 Inhibits NMDA-Stimulated GnRH Secretion: Associated Effects on the Release of Hypothalamic Inhibitory Amino Acid Neurotransmitters

Cited by 22 publications

References 25 publications

How (and why) the immune system makes us sleep

How (and why) the immune system makes us sleep

Inflammation, plasticity and real-time imaging after cerebral ischemia

Interleukin‐1 inhibits firing of serotonergic neurons in the dorsal raphe nucleus and enhances GABAergic inhibitory post‐synaptic potentials

Contact Info

Product

Resources

About