DIURNAL, AGE, AND IMMUNE REGULATION OF INTERLEUKIN-1β AND INTERLEUKIN-1 TYPE 1 RECEPTOR IN THE MOUSE SUPRACHIASMATIC NUCLEUS

Beynon, Amy L.; Coogan, Andrew N.

doi:10.3109/07420528.2010.501927

Cited by 50 publications

(46 citation statements)

References 48 publications

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“…For example, cFOS was increased in the reward circuitry following HFD [120] and in the dorsomedial and lateral hypothalamus [121]. cFOS is similarly induced following LPS treatment in the hypothalamus [122] and this induction is location specific [123]. These studies also postulated that the location is dependent on the neuron function and suggested that cFOS was induced following neuron activation, since cFOS is the most commonly used marker of neuronal activity.…”

Section: Discussionmentioning

confidence: 92%

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

Lainez

Coss²

2019

Neuroendocrinology

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Background: The mechanisms whereby neuroinflammation negatively affects neuronal function in the hypothalamus are not clear. Our previous study determined that obesity-mediated chronic inflammation elicits sex-specific impairment in reproductive function via reduction in spine density in gonadotropin-releasing hormone (GnRH) neurons. Neuroinflammation and subsequent decrease in GnRH neuron spine density was specific for male mice, while protection in females was independent of ovarian estrogens. Methods: To examine if neuroinflammation-induced cytokines can directly regulate GnRH gene expression, herein we examined signaling pathways and mechanisms in males in vivo and in GnRH-expressing cell line, GT1–7. Results: GnRH neurons express cytokine receptors, and chronic or acute neuroinflammation represses GnRH gene expression in vivo. Leukemia inhibitory factor (LIF) in particular represses GnRH expression in GT1–7 cells, while other cytokines do not. STAT3 and MAPK pathways are activated following LIF treatment, but only MAPK pathway, specifically p38α, is sufficient to repress the GnRH gene. LIF induces cFOS that represses the GnRH gene via the -1,793 site in the enhancer region. In vivo, following high-fat diet, cFOS is induced in GnRH neurons and neurons juxtaposed to the leaky blood brain barrier of the organum vasculosum of the lamina terminalis, but not in the neurons further away. Conclusion: Our results indicate that the increase in LIF due to neuroinflammation induces cFOS and represses the GnRH gene. Therefore, in addition to synaptic changes in GnRH neurons, neuroinflammatory cytokines directly regulate gene expression and reproductive function, and the specificity for neuronal targets may stem from the proximity to the fenestrated capillaries.

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Section: Discussionmentioning

confidence: 92%

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

Lainez

Coss²

2019

Neuroendocrinology

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“…One aspect that might be of importance is the role of neuroinflammation in AD on SCN and circadian function. Alzheimer's disease, like many other neurodegenerative diseases, is associated with neuroinflammation (91) which can impact on SCN and circadian function (9,92,93). Another area worthy of further investigation is the role that cholinergic cell loss has in circadian rhythm disturbance in AD and whether anti-cholinesterase drugs might impact on such rhythms in AD.…”

Section: Discussionmentioning

confidence: 99%

The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities

Coogan

Schutová

Husung

et al. 2013

Biological Psychiatry

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148

131

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Alzheimer's disease (AD) is a devastating neurodegenerative condition associated with severe cognitive and behavioral impairments. Circadian rhythms are recurring cycles that display periods of approximately 24 hours and are driven by an endogenous circadian timekeeping system centered on the suprachiasmatic nucleus of the hypothalamus. We review the compelling evidence that circadian rhythms are significantly disturbed in AD and that such disturbance is of significant clinical importance in terms of behavioral symptoms. We also detail findings from neuropathological studies of brain areas associated with the circadian system in postmortem studies, the use of animal models of AD in the investigation of circadian processes, and the evidence that chronotherapeutic approaches aimed at bolstering weakened circadian rhythms in AD produce beneficial outcomes. We argue that further investigation in such areas is warranted and highlight areas for future research that might prove fruitful in ultimately providing new treatment options for this most serious and intractable of conditions.

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“…The timekeeping apparatus of the SCN is a molecular mechanism that involves both transcriptional repressor genes, as well as transcriptional activators, which together create a feedback loop generating circadian oscillations (17). Cytokines such as IL-1 and TNF downregulate the expression of some of these clock genes (6,11). Signaling receptors for IL-1 and TNF are distributed throughout the brain, including the hypothalamus (2, 5), and IL-1 signaling receptors are present in the SCN (6).…”

Section: Discussionmentioning

confidence: 99%

Sepsis-induced alterations in sleep of rats

Baracchi

Ingiosi²,

Raymond³

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Sepsis is a systemic immune response to infection that may result in multiple organ failure and death. Polymicrobial infections remain a serious clinical problem, and in the hospital, sepsis is the number-one noncardiac killer. Although the central nervous system may be one of the first systems affected, relatively little effort has been made to determine the impact of sepsis on the brain. In this study, we used the cecal ligation and puncture (CLP) model to determine the extent to which sepsis alters sleep, the EEG, and brain temperature (Tbr) of rats. Sepsis increases the amount of time rats spend in non-rapid eye movement sleep (NREMS) during the dark period, but not during the light period. Rapid eye movements sleep (REMS) of septic rats is suppressed for about 24 h following CLP surgery, after which REMS increases during dark periods for at least three nights. The EEG is dramatically altered shortly after sepsis induction, as evidenced by reductions in slow-frequency components. Furthermore, sleep is fragmented, indicating that the quality of sleep is diminished. Effects on sleep, the EEG, and Tbr persist for at least 84 h after sepsis induction, the duration of our recording period. Immunohistochemical assays focused on brain stem mechanisms responsible for alterations in REMS, as little information is available concerning infection-induced suppression of this sleep stage. Our immunohistochemical data suggest that REMS suppression after sepsis onset may be mediated, in part, by the brain stem GABAergic system. This study demonstrates for the first time that sleep and EEG patterns are altered during CLP-induced sepsis. These data suggest that the EEG may serve as a biomarker for sepsis onset. These data also contribute to our knowledge of potential mechanisms, whereby infections alter sleep and other central nervous system functions. thermoregulation; behavior; cytokines; circadian rhythms; cecal ligation and puncture SEPSIS RESULTS FROM AN AMPLIFIED inflammatory response to an infectious process that leads to organ dysfunction or risk for secondary infection. As a clinical syndrome, sepsis is defined by the presence of infection and a systemic inflammatory response (7,29). In spite of the ever-increasing sophistication of our antimicrobial armamentarium, sepsis continues to kill millions of people worldwide, and the diagnosis of sepsis still confers a 20 -50% risk of mortality (1, 33). The National Center for Health Statistics now lists sepsis among the top 10 leading causes of death in the United States, and, in fact, sepsis/septic shock is the leading cause of death among patients in noncoronary hospital units (34,48). For those who survive, the impact of severe sepsis does not end with hospital discharge. Mortality from all causes increases from 21% at admission to ϳ75% five years after index admission for severe sepsis (60). Furthermore, survivors of sepsis often suffer from new, persistent, and dramatic cognitive impairment (25). These epidemiologic data demonstrate that sepsis must also be viewed as ...

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DIURNAL, AGE, AND IMMUNE REGULATION OF INTERLEUKIN-1β AND INTERLEUKIN-1 TYPE 1 RECEPTOR IN THE MOUSE SUPRACHIASMATIC NUCLEUS

Cited by 50 publications

References 48 publications

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities

Sepsis-induced alterations in sleep of rats

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