Interleukin-17 affects synaptic plasticity and cognition in an experimental model of multiple sclerosis

Mancini, Andrea; Bellingacci, Laura; Gaetani, Lorenzo; Mazzocchetti, Petra; Zelante, Teresa; Barbera, Livia La; Luca, Antonella De; Tantucci, Michela; Tozzi, Alessandro; Durante, Valentina; Sciaccaluga, Miriam; Megaro, Alfredo; Chiasserini, Davide; Salvadori, Nicola; Lisetti, Viviana; Portaccio, Emilio; Costa, Cinzia; Sarchielli, Paola; Amato, Maria Pia; Parnetti, Lucilla; Viscomi, Maria Teresa; Romani, Luigina; Calabresi, Paolo

doi:10.1016/j.celrep.2021.110094

Cited by 47 publications

(31 citation statements)

References 53 publications

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“…During EAE, meningeal Th17 cells drive neuroinflammation by producing proinflammatory IL17A, further recruitment of leukocytes into the meninges, and induction of follicular meningeal B cell activation [51,52] . A similar phenomenon is recorded in ischemic brain injury models where T cell infiltration and IL17 production drives cerebral infarction [53,54] . IL17A can also be directly recognized by IL17RA expressing hippocampal neurons, which induce dysfunctional hippocampal long-term potentiation and significant cognitive impairments [55] .…”

Section: Meningeal T Cellssupporting

confidence: 63%

The gut-immune-brain axis in neurodevelopment and neurological disorders

Park¹,

Im²

2022

Microbiome Res Rep

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The gut-brain axis is gaining momentum as an interdisciplinary field addressing how intestinal microbes influence the central nervous system (CNS). Studies using powerful tools, including germ-free, antibiotic-fed, and fecal microbiota transplanted mice, demonstrate how gut microbiota perturbations alter the fate of neurodevelopment. Probiotics are also becoming more recognized as potentially effective therapeutic agents in alleviating symptoms of neurological disorders. While gut microbes may directly communicate with the CNS through their effector molecules, including metabolites, their influence on neuroimmune populations, including newly discovered brain-resident T cells, underscore the host immunity as a potent mediator of the gut-brain axis. In this review, we examine the unique immune populations within the brain, the effects of the gut microbiota on the CNS, and the efficacy of specific probiotic strains to propose the novel concept of the gut-immune-brain axis.

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Section: Meningeal T Cellssupporting

confidence: 63%

The gut-immune-brain axis in neurodevelopment and neurological disorders

Park¹,

Im²

2022

Microbiome Res Rep

View full text Add to dashboard Cite

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“…It was also shown that under the hypoxia condition exposure to LPS could depress the post-synaptic efficacy of glutamate receptors by the superoxide and nitric oxide production (Zhang et al, 2014 ). The number of studies on such immune-triggered modulations of synaptic transmission in the CNS is increasing these days (Pascual et al, 2012 ; Parkhurst et al, 2013 ; Zhan et al, 2014 ; Zhang et al, 2014 ; Yamamoto et al, 2019 ; Di Filippo et al, 2021 ). Therefore, brain immunity is the triggering factor of synaptic plasticity via immune receptors, such as pattern-recognition receptors and cytokine receptors, expressed in the neurons.…”

Section: Microglia Heterogeneity and Roles For Modulating Activity Of...mentioning

confidence: 99%

“…Monoclonal anti-IL-17B histochemistry displays its expression in neurons and glial cells in the cerebellum, hippocampus, and cerebral cortex (Moore et al, 2002 ). IL-17A is also studied in the mouse models of neuropathic pain and multiple sclerosis (Luo et al, 2019 ; Di Filippo et al, 2021 ). Luo et al ( 2019 ) demonstrated that IL-17A is mainly released from spinal cord astrocytes, and its receptor IL-17R exists in somatostatin-expressing interneurons.…”

Section: Roles Of Inflammatory Cytokines and Lipid Mediators In Synap...mentioning

confidence: 99%

“…Selective knockdown of IL-17R in spinal somatostatin-expressing interneurons reduces paclitaxel-induced hypersensitivity after paclitaxel and neuropathic pain (Luo et al, 2019 ). According to Di Filippo et al ( 2021 ), the IL-17A receptor (IL-17RA) is highly expressed in neurons in the hippocampal CA1, and exposure to 20 ng/ml IL-17A disrupts hippocampal LTP through the activation of IL-17RA and p38 mitogen-activated protein kinase (MAPK). IL-17A overexpression mimics the disruption of LTP as neurons in the EAE.…”

Section: Roles Of Inflammatory Cytokines and Lipid Mediators In Synap...mentioning

confidence: 99%

“…IL-17A overexpression mimics the disruption of LTP as neurons in the EAE. The loss of IL-17A ameliorates EAE-related cognitive deficits (Di Filippo et al, 2021 ). In contrast, the roles of cerebellar IL-17 are not well-understood yet, and an advance investigation is required.…”

Section: Roles Of Inflammatory Cytokines and Lipid Mediators In Synap...mentioning

confidence: 99%

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Immune-Triggered Forms of Plasticity Across Brain Regions

Hikosaka

Kawano

Wada

et al. 2022

Front. Cell. Neurosci.

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Immune cells play numerous roles in the host defense against the invasion of microorganisms and pathogens, which induces the release of inflammatory mediators (e.g., cytokines and chemokines). In the CNS, microglia is the major resident immune cell. Recent efforts have revealed the diversity of the cell types and the heterogeneity of their functions. The refinement of the synapse structure was a hallmark feature of the microglia, while they are also involved in the myelination and capillary dynamics. Another promising feature is the modulation of the synaptic transmission as synaptic plasticity and the intrinsic excitability of neurons as non-synaptic plasticity. Those modulations of physiological properties of neurons are considered induced by both transient and chronic exposures to inflammatory mediators, which cause behavioral disorders seen in mental illness. It is plausible for astrocytes and pericytes other than microglia and macrophage to induce the immune-triggered plasticity of neurons. However, current understanding has yet achieved to unveil what inflammatory mediators from what immune cells or glia induce a form of plasticity modulating pre-, post-synaptic functions and intrinsic excitability of neurons. It is still unclear what ion channels and intracellular signaling of what types of neurons in which brain regions of the CNS are involved. In this review, we introduce the ubiquitous modulation of the synaptic efficacy and the intrinsic excitability across the brain by immune cells and related inflammatory cytokines with the mechanism for induction. Specifically, we compare neuro-modulation mechanisms by microglia of the intrinsic excitability of cerebellar Purkinje neurons with cerebral pyramidal neurons, stressing the inverted directionality of the plasticity. We also discuss the suppression and augmentation of the extent of plasticity by inflammatory mediators, as the meta-plasticity by immunity. Lastly, we sum up forms of immune-triggered plasticity in the different brain regions with disease relevance. Together, brain immunity influences our cognition, sense, memory, and behavior via immune-triggered plasticity.

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The Use of Stem Cells as a Potential Treatment Method for Selected Neurodegenerative Diseases: Review

et al. 2023

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Stem cells have been the subject of research for years due to their enormous therapeutic potential. Most neurological diseases such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are incurable or very difficult to treat. Therefore new therapies are sought in which autologous stem cells are used. They are often the patient's only hope for recovery or slowing down the progress of the disease symptoms. The most important conclusions arise after analyzing the literature on the use of stem cells in neurodegenerative diseases. The effectiveness of MSC cell therapy has been confirmed in ALS and HD therapy. MSC cells slow down ALS progression and show early promising signs of efficacy. In HD, they reduced huntingtin (Htt) aggregation and stimulation of endogenous neurogenesis. MS therapy with hematopoietic stem cells (HSCs) inducted significant recalibration of pro-inflammatory and immunoregulatory components of the immune system. iPSC cells allow for accurate PD modeling. They are patient—specific and therefore minimize the risk of immune rejection and, in long-term observation, did not form any tumors in the brain. Extracellular vesicles derived from bone marrow mesenchymal stromal cells (BM-MSC-EVs) and Human adipose-derived stromal/stem cells (hASCs) cells are widely used to treat AD. Due to the reduction of Aβ42 deposits and increasing the survival of neurons, they improve memory and learning abilities. Despite many animal models and clinical trial studies, cell therapy still needs to be refined to increase its effectiveness in the human body. Graphical Abstract

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Interleukin-17 affects synaptic plasticity and cognition in an experimental model of multiple sclerosis

Cited by 47 publications

References 53 publications

The gut-immune-brain axis in neurodevelopment and neurological disorders

The gut-immune-brain axis in neurodevelopment and neurological disorders

Immune-Triggered Forms of Plasticity Across Brain Regions

The Use of Stem Cells as a Potential Treatment Method for Selected Neurodegenerative Diseases: Review

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