The role of cytokines in modulating learning and memory and brain plasticity

Bourgognon, Julie-Myrtille; Cavanagh, Jonathan

doi:10.1177/2398212820979802

Cited by 155 publications

(89 citation statements)

References 160 publications

(181 reference statements)

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“…Rather unexpectedly, and although no significant differences in expression were observed in the optic tectum, levels of il-6 were downregulated with age in the killifish retina. This contrasts mammalian models, in which IL-6 expression has been shown to increase in the old brain 68 , 69 , 80 , 81 , 90 , 91 . However, IL-6 is known to have both pro- and anti-inflammatory activities, so it is possible that in the killifish brain, Il-6 mainly acts as an anti-inflammatory cytokine.…”

Section: Discussionmentioning

confidence: 77%

The killifish visual system as an in vivo model to study brain aging and rejuvenation

et al. 2021

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Worldwide, people are getting older, and this prolonged lifespan unfortunately also results in an increased prevalence of age-related neurodegenerative diseases, contributing to a diminished life quality of elderly. Age-associated neuropathies typically include diseases leading to dementia (Alzheimer’s and Parkinson’s disease), as well as eye diseases such as glaucoma and age-related macular degeneration. Despite many research attempts aiming to unravel aging processes and their involvement in neurodegeneration and functional decline, achieving healthy brain aging remains a challenge. The African turquoise killifish (Nothobranchius furzeri) is the shortest-lived reported vertebrate that can be bred in captivity and displays many of the aging hallmarks that have been described for human aging, which makes it a very promising biogerontology model. As vision decline is an important hallmark of aging as well as a manifestation of many neurodegenerative diseases, we performed a comprehensive characterization of this fish’s aging visual system. Our work reveals several aging hallmarks in the killifish retina and brain that eventually result in a diminished visual performance. Moreover, we found evidence for the occurrence of neurodegenerative events in the old killifish retina. Altogether, we introduce the visual system of the fast-aging killifish as a valuable model to understand the cellular and molecular mechanisms underlying aging in the vertebrate central nervous system. These findings put forward the killifish for target validation as well as drug discovery for rejuvenating or neuroprotective therapies ensuring healthy aging.

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Section: Discussionmentioning

confidence: 77%

The killifish visual system as an in vivo model to study brain aging and rejuvenation

et al. 2021

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“…A modern theory hypothesizes that in physiological conditions the proinflammatory cytokines such as IL-1β, IL-6, and TNFα support long-term plasticity and learning and memory processes. On the contrary, when cytokine levels are elevated, such as in models of brain injury or infection or neurodegeneration, the effects of cytokines are mostly detrimental to memory function [82]. In this regard, in APP/PS1 transgenic mice, a model of Alzheimer's disease, chronic treatment with ciproxifan reduced both COX-1 and COX-2 activities, decreased the level of pro-inflammatory cytokines IL-1α, IL-1β, and IL-6, and increased the level of anti-inflammatory cytokine TGF-1β [83].…”

Section: Histamine Deprivation or Potentiation Do Not Affect General Motor Activitymentioning

confidence: 99%

Short- and Long-Term Social Recognition Memory Are Differentially Modulated by Neuronal Histamine

et al. 2021

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The ability of recognizing familiar conspecifics is essential for many forms of social interaction including reproduction, establishment of dominance hierarchies, and pair bond formation in monogamous species. Many hormones and neurotransmitters have been suggested to play key roles in social discrimination. Here we demonstrate that disruption or potentiation of histaminergic neurotransmission differentially affects short (STM) and long-term (LTM) social recognition memory. Impairments of LTM, but not STM, were observed in histamine-deprived animals, either chronically (Hdc−/− mice lacking the histamine-synthesizing enzyme histidine decarboxylase) or acutely (mice treated with the HDC irreversible inhibitor α-fluoromethylhistidine). On the contrary, restriction of histamine release induced by stimulation of the H3R agonist (VUF16839) impaired both STM and LTM. H3R agonism-induced amnesic effect was prevented by pre-treatment with donepezil, an acetylcholinesterase inhibitor. The blockade of the H3R with ciproxifan, which in turn augmented histamine release, resulted in a procognitive effect. In keeping with this hypothesis, the procognitive effect of ciproxifan was absent in both Hdc−/− and αFMH-treated mice. Our results suggest that brain histamine is essential for the consolidation of LTM but not STM in the social recognition test. STM impairments observed after H3R stimulation are probably related to their function as heteroreceptors on cholinergic neurons.

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“…This is in large part due to a long and widely held understanding of the brain as an "immunologically privileged" site in which the neurovasculature, surrounded by a specialized cellular scaffold called the blood-brain barrier (BBB), is largely impenetrable not only to circulating immune cells but to soluble cytokines as well ( 7 ). This classical view has shifted over the past ~15 years thanks in large part to two discoveries: (1) canonical pro-inflammatory cytokines such as TNFα, IFNγ, and IL-1β regulate synaptic transmission between neurons ( 8 , 9 ); [reviewed ( 10 , 11 )], and (2) the resident immune cells and predominant cytokine expressers of the CNS, microglia, play an astoundingly wide array of previously unappreciated roles in the healthy brain ( 12 , 13 ). Yet, it remains to be determined how microglia and cytokines play such specialized roles in the development and function of the CNS compared to their roles in the context of immunity.…”

Section: Introductionmentioning

confidence: 99%

Microglia, Cytokines, and Neural Activity: Unexpected Interactions in Brain Development and Function

Ferro

Auguste²,

Cheadle³

2021

Front. Immunol.

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Intercellular signaling molecules such as cytokines and their receptors enable immune cells to communicate with one another and their surrounding microenvironments. Emerging evidence suggests that the same signaling pathways that regulate inflammatory responses to injury and disease outside of the brain also play powerful roles in brain development, plasticity, and function. These observations raise the question of how the same signaling molecules can play such distinct roles in peripheral tissues compared to the central nervous system, a system previously thought to be largely protected from inflammatory signaling. Here, we review evidence that the specialized roles of immune signaling molecules such as cytokines in the brain are to a large extent shaped by neural activity, a key feature of the brain that reflects active communication between neurons at synapses. We discuss the known mechanisms through which microglia, the resident immune cells of the brain, respond to increases and decreases in activity by engaging classical inflammatory signaling cascades to assemble, remodel, and eliminate synapses across the lifespan. We integrate evidence from (1) in vivo imaging studies of microglia-neuron interactions, (2) developmental studies across multiple neural circuits, and (3) molecular studies of activity-dependent gene expression in microglia and neurons to highlight the specific roles of activity in defining immune pathway function in the brain. Given that the repurposing of signaling pathways across different tissues may be an important evolutionary strategy to overcome the limited size of the genome, understanding how cytokine function is established and maintained in the brain could lead to key insights into neurological health and disease.

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The role of cytokines in modulating learning and memory and brain plasticity

Cited by 155 publications

References 160 publications

The killifish visual system as an in vivo model to study brain aging and rejuvenation

The killifish visual system as an in vivo model to study brain aging and rejuvenation

Short- and Long-Term Social Recognition Memory Are Differentially Modulated by Neuronal Histamine

Microglia, Cytokines, and Neural Activity: Unexpected Interactions in Brain Development and Function

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