JAK2/STAT3 signaling mediates IL-6-inhibited neurogenesis of neural stem cells through DNA demethylation/methylation

Kong, Xuejian; Gong, Zhuo; Zhang, Le; Sun, Xiangdong; Ou, Zhanhui; Xu, Biao; Huang, Jingyi; Long, Dahong; He, Xiaosong; Lin, Xiaohong; Li, Qingqing; Xu, Liping; Xuan, Aiguo

doi:10.1016/j.bbi.2019.01.027

Cited by 63 publications

(41 citation statements)

References 68 publications

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“…However, the detailed mechanism by which these cytokines modulate the expression of transcription factors fundamental for neuronal proper differentiation remains unresolved. Of note, mounting evidence has reported the existence of multiple regulation mechanisms via cytokine signaling [43][44][45][46][47] . IL-6 activates signal transducer and activator of…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, Satb2 expression has shown to be upregulated cell-extrinsically by ciliary neurotrophic factor and leukemia inhibitory factor, which are members of the gp130 cytokine family, in cervical ganglion neurons undergoing neurotransmitter trans-specification 43 , suggesting that IL-6, which converges on the gp130 pathway, may enhance the transcription of Satb2 in CP neurons. In addition, previous studies have revealed that IL-6, via the JAK2/STAT3 signaling pathway, upregulates DNA methyltransferase 1 and downregulates ten-eleven translocation 3, causing the DNA methylation of Neu-roD1 and resulting in the switch from neurogenesis to astrogliogenesis 44,45 . Meanwhile, IFN-I leads to STAT1 and STAT2 activation via TYK2 and JAK1 and induces the expression of IFN-stimulated genes 39 .…”

Section: Cux1-alexa488mentioning

confidence: 99%

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Transient microglial absence assists postmigratory cortical neurons in proper differentiation

et al. 2020

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In the developing cortex, postmigratory neurons accumulate in the cortical plate (CP) to properly differentiate consolidating subtype identities. Microglia, despite their extensive surveying activity, temporarily disappear from the midembryonic CP. However, the mechanism and significance of this absence are unknown. Here, we show that microglia bidirectionally migrate via attraction by CXCL12 released from the meninges and subventricular zone and thereby exit the midembryonic CP. Upon nonphysiological excessive exposure to microglia in vivo or in vitro, young postmigratory and in vitro-grown CP neurons showed abnormal differentiation with disturbed expression of the subtype-associated transcription factors and genes implicated in functional neuronal maturation. Notably, this effect is primarily attributed to interleukin 6 and type I interferon secreted by microglia. These results suggest that "sanctuarization" from microglia in the midembryonic CP is required for neurons to appropriately fine-tune the expression of molecules needed for proper differentiation, thus securing the establishment of functional cortical circuit.

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Section: Discussionmentioning

confidence: 99%

Section: Cux1-alexa488mentioning

confidence: 99%

Transient microglial absence assists postmigratory cortical neurons in proper differentiation

et al. 2020

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“…JAK2 represents the Janus kinase (JAK) family and is activated at the Tyr1007 site by IL-1β, IL-6, and TNF-α. Phosphorylated JAK2 promotes the activation of STAT3 at the Tyr705 site, which nally leads to neuroin ammation and apoptosis [48][49][50]. There is evidence showing that the signaling pathway related to JAK2/STAT3 is activated in AD, and the inhibition of this signaling pathway can alleviate neuroin ammation in AD [23,51].…”

Section: Discussionmentioning

confidence: 99%

Suan-Zao-Ren Decoction Ameliorate Synaptic Plasticity Through the Inhibition of JAK2/STAT3 Signaling Pathway in APP/PS1 Transgenic Mice

Long

et al. 2020

Preprint

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Background: Suan-Zao-Ren Decoction (SZRD) has been widely used to treat neurological illnesses, like dementia, insomnia, and depression. However, mechanisms underlying SZRD’s improvement in cognitive function remains unclear. In this study, we examined SZRD’s effect on APP/PS1 transgenic mice as well as mechanisms associated with SZRD’s action in alleviating neuroinflammation and improving the synaptic plasticity. Methods: The APP/PS1 mice were treated with different dosages of SZRD (12.96 and 25.92 g/kg/d, in L-SZRD and H-SZRD groups, respectively) for four weeks. Morris water maze was conducted to determine changes in behaviors of the mice after the treatment. Meanwhile, in the samples of the hippocampus, Nissl staining and Golgi-Cox staining were used to detect the synaptic plasticity, Western blot (WB) was employed to test expressions of Aβ1-42, APP, ADAM10, BACE1, PS1, IDE, IBA1, GFAP, PSD95 and SYN, as well as the expressions of JAK2, STAT3 and their phosphorylation patterns to detect involvement of JAK2/STAT3 pathway. Besides, we examined the serum contents of IL-1β, IL-6, and TNF-α using ELISA.Results: Compared to the APP/PS1 mice without any treatment, SZRD, especially the L-SZRD, significantly ameliorated cognitive impairment of the APP/PS1 mice with decreases in the loss of neurons and Aβ plaque deposition as well as improvement of synaptic plasticity in the hippocampus (all P<0.05). Also, SZRD, in particular, the L-SZRD markedly inhibited the serum IL-6, IL-1β, and TNF-α, while reducing the expression of p-JAK2-Tyr1007 and p-STAT3-Tyr705 in the hippocampus of the APP/PS1 mice (all P<0.05). Conclusion: The SZRD, especially the L-SZRD, may improve the cognitive impairment and ameliorate the neural degeneration in APP/PS1 transgenic mice through decreasing Aβ accumulation and inhibiting neuroinflammation via JAK2/STAT3 pathway.

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“…As described previously (Gong et al, 2019;Kong et al, 2019), male mice were anesthetized with 1% pentobarbital sodium and perfused intracardially with saline, followed by 4% paraformaldehyde in 0.1M phosphate buffer in 1 h after fear retrieval test. The brain was removed and immersed overnight in 4% paraformaldehyde in 0.1M phosphate buffer and then placed in 30% sucrose/phosphate buffer for cryoprotection.…”

Section: Immunofluorescencementioning

confidence: 99%

Social Company by a Receptive Mating Partner Facilitates Fear Extinction

et al. 2020

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Fear extinction remains an unresolved challenge for behavioral exposure therapy in patients with post-traumatic stress disorder (PTSD). Previous reports have suggested that social support from either familiar or unfamiliar same-sex partners is beneficial to attenuating fear responses during fear extinction and renewal. Despite that, few studies have examined the effects of social support in advance on fear extinction and/or retrieval. It is also not clear whether social company by a receptive mating partner in advance facilitates fear extinction. In the present study, we address these questions by introducing a co-housing method, where fear-conditioned male mice are co-housed with or without a receptive mating partner prior to fear extinction. We found that while co-housing with an ovariectomized female mouse showed little effect on fear extinction or retrieval, social company by a receptive mating partner in advance dramatically facilitates fear extinction. In addition, the number of cFos-positive neurons in the basolateral amygdala (BLA) were also found to be reduced in male mice accompanied with receptive mating partner in response to fear extinction and retrieval, indicating diminished neuronal activation. Electrophysiological studies further showed that the excitability of excitatory neurons in BLA was decreased, which is probably due to the attenuated basal level of excitatory synaptic transmission. Together, our observations demonstrate an effect of social company by a receptive mating partner can facilitate fear extinction and afford a possible cellular mechanism.

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JAK2/STAT3 signaling mediates IL-6-inhibited neurogenesis of neural stem cells through DNA demethylation/methylation

Cited by 63 publications

References 68 publications

Transient microglial absence assists postmigratory cortical neurons in proper differentiation

Transient microglial absence assists postmigratory cortical neurons in proper differentiation

Suan-Zao-Ren Decoction Ameliorate Synaptic Plasticity Through the Inhibition of JAK2/STAT3 Signaling Pathway in APP/PS1 Transgenic Mice

Social Company by a Receptive Mating Partner Facilitates Fear Extinction

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JAK2/STAT3 signaling mediates IL-6-inhibited neurogenesis of neural stem cells through DNA demethylation/methylation

Cited by 63 publications

References 68 publications

Transient microglial absence assists postmigratory cortical neurons in proper differentiation

Transient microglial absence assists postmigratory cortical neurons in proper differentiation

Suan-Zao-Ren Decoction&nbsp;Ameliorate&nbsp;Synaptic Plasticity Through&nbsp;the Inhibition of JAK2/STAT3 Signaling Pathway&nbsp;in APP/PS1 Transgenic Mice

Social Company by a Receptive Mating Partner Facilitates Fear Extinction

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Suan-Zao-Ren Decoction Ameliorate Synaptic Plasticity Through the Inhibition of JAK2/STAT3 Signaling Pathway in APP/PS1 Transgenic Mice