Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

Sun, Li; Han, Ruili; Guo, Fei; Chen, Hai; Wang, Wen; Chen, Ziyang; Liu, Wei; Sun, Xude; Gao, Changjun

doi:10.1038/s41420-020-00298-8

Cited by 28 publications

(20 citation statements)

References 69 publications

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“…Indeed, previous studies have demonstrated the inhibitory effect of IL-17 on neurogenesis, in particular, on neural progenitor proliferation in vivo and in vitro [23,34,[42][43][44][45].…”

Section: Discussionmentioning

confidence: 97%

Interleukine-17 Modulates Neurogenesis and Behavior Following Exposure to Trauma in Mice

Willinger

Turgeman

2022

Cells

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Post-traumatic stress disorder (PTSD) is a psychiatric disorder accompanied by deficits in cognitive and social skills. Adult hippocampal neurogenesis is a lifelong phenomenon, with new neurons being formed in the granular cell layer of the dentate gyrus. Impaired neurogenesis is associated with multiple behavioral disorders including Alzheimer’s disease and schizophrenia. PTSD patients often present hippocampal atrophy and animal models clearly present impaired neurogenesis. Previous studies on PTSD patients demonstrated elevated levels of Th17 cells and plasma levels of the pro-inflammatory cytokine interleukin-17A (IL-17A). Since IL-17A can impair neurogenesis in mice, we thus hypothesized that decreasing the serum levels of IL-17A will increase hippocampal neurogenesis and alleviate symptoms in a murine model of PTSD. Surprisingly, our results showed that attempting to neutralize IL-17A with an antibody resulted in increased serum levels of IL-17A, while targeting IL-23, the upstream regulator of IL-17, did lower the levels of IL-17A in trauma-exposed mice. As expected, increased levels of serum IL-17A (in anti-IL-17A treated mice) resulted in impaired neurogenesis, reflected by reduced number of proliferating Ki67+ neural progenitors and newly formed DCX+ neurons, which was correlated with increased expression of HES1. Nevertheless, increased maturation was noted by the expression of SLIT2 and ACHE. In contrast, treatment with anti-IL-23 indeed resulted in increased neurogenesis. Behaviorally, both treatments did not affect trauma-related freezing behavior but did affect trauma-related social deficits. Unexpectedly, increased levels of serum IL-17A (in anti-IL-17A treated mice) prevented social deficits in trauma-exposed mice while anti-IL-23 exacerbated these deficits. We thus conclude that IL-17 is involved in regulating neurogenesis following exposure to stress but may be important in maintaining social behavior.

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“…Indeed, previous studies have demonstrated the inhibitory effect of IL-17 on neurogenesis, in particular, on neural progenitor proliferation in vivo and in vitro [23,34,[42][43][44][45].…”

Section: Discussionmentioning

confidence: 97%

Interleukine-17 Modulates Neurogenesis and Behavior Following Exposure to Trauma in Mice

Willinger

Turgeman

2022

Cells

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“…In addition to its potential role in regulating the immune response to balance cytotoxic and tolerant immune profiles, it also results in acute injury. As a proinflammatory cytokine, IL-17 essentially incorporates a complicated network of cytokines that is responsible for various inflammatory conditions and pathogenesis (11)(12)(13)(14). The inflammatory response and cytokine production are particularly crucial in the progression of AP.…”

Section: Introductionmentioning

confidence: 99%

Role of Interleukin-17 in Acute Pancreatitis

Chen

Liu

et al. 2021

Front. Immunol.

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Acute pancreatitis (AP) is a leading cause of death and is commonly accompanied by systemic manifestations that are generally associated with a poor prognosis. Many cytokines contribute to pancreatic tissue damage and cause systemic injury. Interleukin-17 (IL-17) is a cytokine that may play a vital role in AP. Specifically, IL-17 has important effects on the immune response and causes interactions between different inflammatory mediators in the AP-related microenvironment. In this literature review, we will discuss the existing academic understanding of IL-17 and the impacts of IL-17 in different cells (especially in acinar cells and immune system cells) in AP pathogenesis. The clinical significance and potential mechanisms of IL-17 on AP deterioration are emphasized. The evidence suggests that inhibiting the IL-17 cytokine family could alleviate the pathogenic process of AP, and we highlight therapeutic strategies that directly or indirectly target IL-17 cytokines in acute pancreatitis.

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“…Knockout of IL-17 helps to regulate the PI3K-Akt pathway, promotes the proliferation of NSCs, and promotes nerve growth after IS. [ 22 ] This study found that the RPR-FC has neuroprotective effects, promoting nerve repair, vascular remodeling, inhibition of neuronal apoptosis, and regulation of inflammatory factor expression after IS.…”

Section: Resultsmentioning

confidence: 99%

To explore the Radix Paeoniae Rubra-Flos Carthami herb pair's potential mechanism in the treatment of ischemic stroke by network pharmacology and molecular docking technology

Chen

Wang

et al. 2021

Medicine

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To explore the Radix Paeoniae Rubra-Flos Carthami herb pair's (RPR-FC) potential mechanism in treating ischemic stroke (IS) by network pharmacology and molecular docking technology. The Traditional Chinese Medicine Systems Pharmacology Database was used to screen the active components of the RPR-FC, and Cytoscape 3.8 software was used to construct a network map of its active components and targets of action. The GeneCards and OMIM databases were used to identify disease targets of IS, and the common targets were chosen as research targets and imported into the STRING database to construct a protein–protein interaction network map of these targets. R language software was used to analyze the enrichment of GO terms and KEGG pathways, and explore the mechanisms of these targets. Molecular docking technology was used to verify that the RPR-FC components had a good bonding activity with their potential targets. A total of 44 active components, which corresponded to 197 targets, were identified in the RPR-FC. There were 139 common targets between the herb pair and IS. GO functional enrichment analysis revealed 2253 biological process entries, 72 cellular components entries, and 183 molecular functions entries. KEGG pathway enrichment analysis was mainly related to the NF-kappa B signaling pathway, the TNF signaling pathway, apoptosis, the MAPK signaling pathway, the PI3K-Akt signaling pathway, the VEGF signaling pathway, etc. The molecular docking results showed the components that docked well with key targets were quercetin, luteolin, kaempferol, and baicalein. The active components (quercetin, luteolin, kaempferol, and baicalein) of the RPR-FC and their targets act on proteins such as MAPK1, AKT1, VEGFA, and CASP3, which are closely related to IS. 1 These targets are closely related to the NF-kappa B signaling pathway, the MAPK signaling pathway, the PI3K-Akt signaling pathway, the VEGF signaling pathway, and other signaling pathways. These pathways are involved in the recovery of nerve function, angiogenesis, and neuronal apoptosis and the regulation of inflammatory factors, which may have a therapeutic effect on IS.

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Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

Cited by 28 publications

References 69 publications

Interleukine-17 Modulates Neurogenesis and Behavior Following Exposure to Trauma in Mice

Interleukine-17 Modulates Neurogenesis and Behavior Following Exposure to Trauma in Mice

Role of Interleukin-17 in Acute Pancreatitis

To explore the Radix Paeoniae Rubra-Flos Carthami herb pair's potential mechanism in the treatment of ischemic stroke by network pharmacology and molecular docking technology

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