IL-1/IL-1ra balance in the brain revisited – Evidence from transgenic mouse models

Spulber, Ştefan; Bartfai, Tamás; Schultzberg, Marianne

doi:10.1016/j.bbi.2009.02.015

Cited by 71 publications

(68 citation statements)

References 72 publications

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“…The effects are consistent with the tight negative regulation of cytokine activity by endogenous receptor antagonists (IL-1ra) (Spulber, Bartfai, & Schultzberg, 2009a) and decoy receptors (IL-1R2) (Garlanda, Dinarello, & Mantovani, 2013). Further supporting the synergistic role of interactions between IL-1β and IL-1ra is the finding that despite the impairing effects of either on their own, application of IL-1β and IL-1ra together normalizes the maintenance of LTP (A.…”

Section: Modulation Of Memory By Cytokinessupporting

confidence: 71%

Modulation of learning and memory by cytokines: Signaling mechanisms and long term consequences

Donzis

Tronson

2014

Neurobiology of Learning and Memory

227

154

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This review describes the role of cytokines and their downstream signaling cascades on the modulation of learning and memory. Immune proteins are required for many key neural processes and dysregulation of these functions by systemic inflammation can result in impairments of memory that persist long after the resolution of inflammation. Recent research has demonstrated that manipulations of individual cytokines can modulate learning, memory, and synaptic plasticity. The many conflicting findings, however, have prevented a clear understanding of the precise role of cytokines in memory. Given the complexity of inflammatory signaling, understanding its modulatory role requires a shift in focus from single cytokines to a network of cytokine interactions and elucidation of the cytokine-dependent intracellular signaling cascades. Finally, we propose that whereas signal transduction and transcription may mediate short-term modulation of memory, long-lasting cellular and molecular mechanisms such as epigenetic modifications and altered neurogenesis may be required for the long lasting impact of inflammation on memory and cognition.

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Section: Modulation Of Memory By Cytokinessupporting

confidence: 71%

Modulation of learning and memory by cytokines: Signaling mechanisms and long term consequences

Donzis

Tronson

2014

Neurobiology of Learning and Memory

227

154

View full text Add to dashboard Cite

show abstract

“…Animal studies also revealed that this cytokine supports memory formation and underlying synaptic plasticity (del Rey et al, 2013;Goshen et al, 2007;Schneider et al, 1998;Spulber et al, 2009). In the present study, we tested the effects of inhibiting IL-1 signaling by the IL-1ra anakinra on sleep and sleep-dependent memory consolidation for the first time in healthy humans.…”

Section: Discussionmentioning

confidence: 93%

Effects of an interleukin-1 receptor antagonist on human sleep, sleep-associated memory consolidation, and blood monocytes

Schmidt

Linz

Diekelmann

et al. 2015

Brain, Behavior, and Immunity

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Pro-inflammatory cytokines like interleukin-1 beta (IL-1) are major players in the interaction between the immune system and the central nervous system. Various animal studies report a sleep-promoting effect of IL-1 leading to enhanced slow wave sleep (SWS). Moreover, this cytokine was shown to affect hippocampus-dependent memory. However, the role of IL-1 in human sleep and memory is not yet understood. We administered the synthetic IL-1 receptor antagonist anakinra (IL-1ra) in healthy humans (100mg, subcutaneously, before sleep; n=16) to investigate the role of IL-1 signaling in sleep regulation and sleep-dependent declarative memory consolidation. Inasmuch monocytes have been considered a model for central nervous microglia, we monitored cytokine production in classical and non-classical blood monocytes to gain clues about how central nervous effects of IL-1ra are conveyed. Contrary to our expectation, IL-1ra increased EEG slow wave activity during SWS and non-rapid eye movement (NonREM) sleep, indicating a deepening of sleep, while sleep-associated memory consolidation remained unchanged. Moreover, IL-1ra slightly increased prolactin and reduced cortisol levels during sleep. Production of IL-1 by classical monocytes was diminished after IL-1ra. The discrepancy to findings in animal studies might reflect species differences and underlines the importance of studying cytokine effects in humans.

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“…The effect of IL-1β on LTP is dose-dependent Some time after the initial findings that indicated a negative effect of IL-1β on LTP, a number of papers provided data demonstrating that the IL-1β-induced change is probably dosedependent since blocking IL-1R by IL-1ra also decreased LTP (Goshen et al, 2007;Loscher et al, 2003;Schneider et al, 1998;Spulber et al, 2009) and a temperature-dependent effect of IL-1ra on LTP was also described (Ross et al, 2003). It was therefore suggested that physiological levels of IL-1 are necessary for induction and maintenance of LTP and this was confirmed by Avital and colleagues who showed that LTP was absent in perforant path granule cell synapses in anaesthetized IL-1R knockout mice and also in area CA1 in slices prepared from these mice (Avital et al, 2003).…”

mentioning

confidence: 96%

Neuroinflammatory changes negatively impact on LTP: A focus on IL-1β

Lynch

2015

Brain Research

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IL-1/IL-1ra balance in the brain revisited – Evidence from transgenic mouse models

Cited by 71 publications

References 72 publications

Modulation of learning and memory by cytokines: Signaling mechanisms and long term consequences

Modulation of learning and memory by cytokines: Signaling mechanisms and long term consequences

Effects of an interleukin-1 receptor antagonist on human sleep, sleep-associated memory consolidation, and blood monocytes

Neuroinflammatory changes negatively impact on LTP: A focus on IL-1β

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