Interleukin-17 inhibits Adult Hippocampal Neurogenesis

Liu, Qiangqiang; Wei, Xianzhu; He, Ping; Turner, Dharshaun; Yin, Jun; Gan, Yunhua; Shi, Fu‐Dong; Wu, Jie

doi:10.1038/srep07554

Cited by 85 publications

(77 citation statements)

References 53 publications

(68 reference statements)

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“…The alterations in time-dependent facilitation observed in Fgf14 −/− animals are consistent with synaptic input remodeling of the DG circuit, such as granule cell axonal sprouting, homeostatic changes driven by GABAergic inputs or modifications of the release machinery and excitatory pre-synaptic terminals (65, 66). These phenotypes suggest that altered neurogenesis might lead to an over-excitable DG circuit, more prone to an epileptic-like status, or locked in an immature stage (66–68). Future studies are required to confirm this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 14 Modulates the Neurogenesis of Granule Neurons in the Adult Dentate Gyrus

Alshammari

Nenov

et al. 2015

Mol Neurobiol

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Adult neurogenesis, the production of mature neurons from progenitor cells in the adult mammalian brain, is linked to the etiology of neurodegenerative and psychiatric disorders. However, a thorough understanding of the molecular elements at the base of adult neurogenesis remains elusive. Here, we provide evidence for a previously undescribed function of fibroblast growth factor 14 (FGF14), a brain disease-associated factor that controls neuronal excitability and synaptic plasticity, in regulating adult neurogenesis in the dentate gyrus (DG). We found that FGF14 is dynamically expressed in restricted subtypes of Sex Determining Region Y-Box 2 (Sox2) positive and doublecortin (DCX) positive neural progenitors in the DG. BrdU incorporation studies and confocal imaging revealed that genetic deletion of Fgf14 in Fgf14−/− mice leads to a significant change in the proportion of proliferating, and immature and mature newly born adult granule cells. This results in an increase in the late immature and early mature population of DCX and calretinin (CR) positive neurons. Electrophysiological extracellular field recordings showed reduced minimal threshold response and impaired paired-pulse facilitation at the perforant path to DG inputs in Fgf14−/− compared to Fgf14+/+ mice, supporting disrupted synaptic connectivity as a correlative read-out to impaired neurogenesis. These new insights into the biology of FGF14 in neurogenesis shed light into the signaling pathways associated with disrupted functions in complex brain diseases.

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Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 14 Modulates the Neurogenesis of Granule Neurons in the Adult Dentate Gyrus

Alshammari

Nenov

et al. 2015

Mol Neurobiol

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“…The software was also used to confirm in three dimensions that cells were double-labeled. BrdU-retaining cells in lateral SVZ regions were counted in the same sections used for the analysis 35,36,43 . Quantification was performed in a double-blinded manner.…”

Section: Methodsmentioning

confidence: 99%

Neural stem cells sustain natural killer cells that dictate recovery from brain inflammation

et al. 2016

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Recovery from organ-specific autoimmune diseases largely relies on the mobilization of endogenous repair mechanisms and local factors that control them. Natural killer (NK) cells are swiftly mobilized to organs targeted by autoimmunity and typically undergo numerical contraction when inflammation wanes. We report the unexpected finding that NK cells are retained in the brain subventricular zone (SVZ) during the chronic phase of multiple sclerosis in humans and its animal model in mice. These NK cells were found preferentially in close proximity to SVZ neural stem cells (NSCs) that produce interleukin-15 and sustain functionally competent NK cells. Moreover, NK cells limited the reparative capacity of NSCs following brain inflammation. These findings reveal that reciprocal interactions between NSCs and NK cells regulate neurorepair.

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“…Genetic deletion of IL-17 increased the number of adult-born neurons. Furthermore, IL-17 deletion altered the network of the cytokines, facilitated basal excitatory synaptic transmission, enhanced intrinsic neuronal excitability, and increased expression of proneuronal genes in neuronal progenitor cells (NPCs), suggesting a profound role of IL-17 in the negative regulation of adult hippocampal neurogenesis under physiology conditions 93 . In an ischemic brain injury model, IL-17, highly expressed by γδ T lymphocytes, has been shown to play an important role in mediating the evolution of brain infarction and accompanying neurological deficits in the delayed phase of injury 94 .…”

Section: Evidence Of the Role Of Il-17 Signaling Pathway In Aldmentioning

confidence: 99%

The Role of IL-17 Signaling in Regulation of the Liver–Brain Axis and Intestinal Permeability in Alcoholic Liver Disease

Liu

et al. 2016

Curr Pathobiol Rep

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Alcoholic liver disease (ALD) progresses from a normal liver, to steatosis, steatohepatitis, fibrosis and hepatocellular carcinoma (HCC). Despite intensive studies, the pathogenesis of ALD is poorly understood, in part due to a lack of suitable animal models which mimic the stages of ALD progression. Furthermore, the role of IL-17 in ALD has not been evaluated. We and others have recently demonstrated that IL-17 signaling plays a critical role in development of liver fibrosis and cancer. Here we summarize the most recent evidence supporting the role of IL-17 in ALD. As a result of a collaborative effort of Drs. Karin, Gao, Tsukamoto and Kisseleva, we developed several improved models of ALD in mice: 1) chronic-plus-binge model that mimics early stages of steatohepatitis, 2) intragastric ethanol feeding model that mimics alcoholic steatohepatitis and fibrosis, and 3) diethylnitrosamine (DEN)+alcohol model that mimics alcoholic liver cancer. These models might provide new insights into the mechanism of IL-17 signaling in ALD and help identify novel therapeutic targets.

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Interleukin-17 inhibits Adult Hippocampal Neurogenesis

Cited by 85 publications

References 53 publications

Fibroblast Growth Factor 14 Modulates the Neurogenesis of Granule Neurons in the Adult Dentate Gyrus

Fibroblast Growth Factor 14 Modulates the Neurogenesis of Granule Neurons in the Adult Dentate Gyrus

Neural stem cells sustain natural killer cells that dictate recovery from brain inflammation

The Role of IL-17 Signaling in Regulation of the Liver–Brain Axis and Intestinal Permeability in Alcoholic Liver Disease

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