Role of Proinflammatory Cytokines on Lipopolysaccharide-Induced Phase Shifts in Locomotor Activity Circadian Rhythm

Leone, María Juliana; Marpegan, Luciano; Duhart, José M.; Golombék, Diego A.

doi:10.3109/07420528.2012.682681

Cited by 41 publications

(48 citation statements)

References 40 publications

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“…Moreover, interleukin-2 and TNF-alpha have been shown to alter sleep architecture in humans (Kapsimalis et al 2005;Opp 2005). The cytokine hypothesis might provide possible intervention targets for future drugs, since it has been already demonstrated that administration of soluble TNF-alpha receptor (soluble receptor binds to the cytokine and neutralizes it) prevents phase shift in locomotor activity in rats (Leone et al 2012;Paladino et al 2014). Translating these findings to human studies may alleviate circadian disruptions and the cluster of symptoms that often accompany patients with cancer.…”

Section: Discussionmentioning

confidence: 94%

Circadian rhythms measured by actigraphy during oncological treatments: a systematic review

Huang

Madsen

Gögenür

2015

Biological Rhythm Research

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During oncological treatment patients often suffer from fatigue, insomnia, and daytime inactivity. This cluster of symptoms and overall survival are linked with circadian rhythm disruptions in rest-activity, which can be objectively characterized using actigraphy. We systematically reviewed the body of literature using actigraphy to characterize the circadian rhythm disruption in patients during oncological treatments and studies that introduced interventions to deal with this disruption. Thirteen observational and two interventional studies were included in this review. These mainly described patients with breast cancer undergoing chemotherapy, and the disruptions were persistent among these patients, and the disruptions peaked at the start of chemotherapy cycles and decreased during the periods in between. Light and behavioral therapy showed some alleviating effects in patients with breast cancer. We also found that circadian rhythm disruptions were prevalent in patients during other cancer therapies. Effective cancer therapy controls cancer growth and improves circadian organization. Cancer therapy itself, however, also contributes to cancer associated circadian dys-synchrony. Interrupting this vicious cycle represents an important opportunity for diminishing cancer patients' suffering and improving or even prolonging their useful and enjoyable lives.

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Section: Discussionmentioning

confidence: 94%

Circadian rhythms measured by actigraphy during oncological treatments: a systematic review

Huang

Madsen

Gögenür

2015

Biological Rhythm Research

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“…Moreover, activation of the immune system can also modulate the circadian clock. Peripheral LPS administration or introcerebroventricular (icv) injection of TNF-α or IL-1β produced phase delays in wheel running activity [17,39], and icv delivery of a proinflammatory cocktail also activated c-Fos expression in the SCN [40]. In addition, clock gene expression can be altered by exposure to different proinflammatory factors [41-44].…”

Section: Discussionmentioning

confidence: 99%

Characterization of locomotor activity circadian rhythms in athymic nude mice

Paladino¹,

Duhart²,

Fedele³

et al. 2013

J Circadian Rhythms

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BackgroundThe relation between circadian dysregulation and cancer incidence and progression has become a topic of major interest over the last decade. Also, circadian timing has gained attention regarding the use of chronopharmacology-based therapeutics. Given its lack of functional T lymphocytes, due to a failure in thymus development, mice carrying the Foxn1(Δ/Δ) mutation (nude mice) have been traditionally used in studies including implantation of xenogeneic tumors. Since the immune system is able to modulate the circadian clock, we investigated if there were alterations in the circadian system of the athymic mutant mice.MethodsGeneral activity circadian rhythms in 2–4 month-old Foxn1(Δ/Δ) mice (from Swiss Webster background) and their corresponding wild type (WT) controls was recorded. The response of the circadian system to different manipulations (constant darkness, light pulses and shifts in the light–dark schedule) was analyzed.ResultsFree-running periods of athymic mice and their wild type counterpart were 23.86 ± 0.03 and 23.88 ± 0.05 hours, respectively. Both strains showed similar phase delays in response to 10 or 120 minutes light pulses applied in the early subjective night and did not differ in the number of c-Fos-expressing cells in the suprachiasmatic nuclei, after a light pulse at circadian time (CT) 15. Similarly, the two groups showed no significant difference in the time needed for resynchronization after 6-hour delays or advances in the light–dark schedule. The proportion of diurnal activity, phase-angle with the zeitgeber, subjective night duration and other activity patterns were similar between the groups.ConclusionsSince athymic Foxn1(Δ/Δ) mice presented no differences with the WT controls in the response of the circadian system to the experimental manipulations performed in this work, we conclude that they represent a good model in studies that combine xenograft implants with either alteration of the circadian schedules or chronopharmacological approaches to therapeutics.

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“…Also, the sleep-wake cycle (partially controlled by the circadian clock) is modulated by immune factors, including TNF-α and IL-1β (10), and SCN physiology can be altered by infections that alter sleep architecture (11, 12). The presence of receptors for the proinflammatory cytokines TNF-α and IL-1β has been reported in the SCN (13, 14) and immune stimuli have been shown to modulate the phase of the master circadian clock (15–17). Interestingly, the circadian response to a peripheral immune challenge is mediated by the action of TNF-α at the SCN level (15) suggesting an important role for this cytokine in immune-circadian communication.…”

Section: Introductionmentioning

confidence: 99%

“…The presence of receptors for the proinflammatory cytokines TNF-α and IL-1β has been reported in the SCN (13, 14) and immune stimuli have been shown to modulate the phase of the master circadian clock (15–17). Interestingly, the circadian response to a peripheral immune challenge is mediated by the action of TNF-α at the SCN level (15) suggesting an important role for this cytokine in immune-circadian communication.…”

Section: Introductionmentioning

confidence: 99%

Suprachiasmatic Astrocytes Modulate the Circadian Clock in Response to TNF-α

Duhart

Leone

Paladino

et al. 2013

The Journal of Immunology

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The immune and the circadian systems interact in a bidirectional fashion. The master circadian oscillator, located in the suprachiasmatic nuclei of the hypothalamus (SCN), responds to peripheral and local immune stimuli, such as proinflammatory cytokines and bacterial endotoxin. Astrocytes exert several immune functions in the central nervous system and there is growing evidence that points towards a role of these cells in the regulation of circadian rhythms. The aim of this work was to assess the response of SCN astrocytes to immune stimuli, particularly to the proinflammatory cytokine TNF-α. TNF-α applied to cultures of SCN astrocytes from Per2luc knock in mice altered both the phase and amplitude of PER2 expression rhythms, in a phase dependent manner. Furthermore, conditioned media from SCN astrocytes cultures transiently challenged with TNF-α induced an increase in Per1 expression in NIH 3T3 cells, that was blocked by TNF-α antagonism. In addition, these conditioned media could induce phase shifts in SCN PER2 rhythms and, when administered intracerebroventricularly, induced phase delays in behavioral circadian rhythms and SCN activation in control mice, but not in TNF-Receptor-1 mutants. In summary, our results show that TNF-α modulates the molecular clock of SCN astrocytes in vitro and also that, in response to this molecule, SCN astrocytes can modulate clock gene expression in other cells and tissues, and induce phase shifts in a circadian behavioral output in vivo. These findings suggest a role for astroglial cells in the alteration of circadian timing by immune activation.

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Role of Proinflammatory Cytokines on Lipopolysaccharide-Induced Phase Shifts in Locomotor Activity Circadian Rhythm

Cited by 41 publications

References 40 publications

Circadian rhythms measured by actigraphy during oncological treatments: a systematic review

Circadian rhythms measured by actigraphy during oncological treatments: a systematic review

Characterization of locomotor activity circadian rhythms in athymic nude mice

Suprachiasmatic Astrocytes Modulate the Circadian Clock in Response to TNF-α

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