Hippocampal neurogenesis dysfunction linked to depressive-like behaviors in a neuroinflammation induced model of depression

Tang, Mingming; Lin, Wei; Pan, Yuqin; Guan, Xi-ting; Li, Yingcong

doi:10.1016/j.physbeh.2016.04.034

Cited by 78 publications

(55 citation statements)

References 47 publications

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“…In the present study, we found that CSDS resulted in depressivelike behaviors including increased immobility duration in FST, decreased social interaction ratio in SIT, and decreased time spent in the light area in LDT, accompanied by increased TLR4 protein level in hippocampus. Hippocampus is considered to be one of the most (Kubera, Obuchowicz, Goehler, Brzeszcz, & Maes, 2011;Tang et al, 2016;Zhang, Zhang, & You, 2018;Zhao et al, 2019). In this study, by using the antidepressant fluoxetine, TLR4 inhibitor, and TLR4 knockout Con, control; KO, knockout; SD, stress; TNF-α, tumor necrosis factor-α; TLR4, Toll-like receptor 4; WT, wild-type mice, our results suggest that hippocampal TLR4 is involved in behavioral despair induced by CSDS.…”

Section: Discussionmentioning

confidence: 72%

“…Hippocampus is considered to be one of the most important areas involved in stress and depression. For example, neuroinflammation, apoptosis, reduced neurogenesis, and dysfunction of microglia in hippocampus are associated with depression (Kubera, Obuchowicz, Goehler, Brzeszcz, & Maes, ; Tang et al, ; Zhang, Zhang, & You, ; Zhao et al, ). In this study, by using the antidepressant fluoxetine, TLR4 inhibitor, and TLR4 knockout mice, our results suggest that hippocampal TLR4 is involved in behavioral despair induced by CSDS.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, a decrease in depressive symptoms is coupled with a normalization of pro‐inflammatory cytokines levels (Liu, Buisman‐Pijlman, & Hutchinson, ). Animal studies have also shown that pro‐inflammatory cytokines mediate depressive‐like behaviors induced by stress, and administration of cytokine‐inducer lipopolysaccharide (LPS) is sufficient to induce depressive‐like behaviors (Fleshner, Frank, & Maier, ; Tang, Lin, Pan, Guan, & Li, ).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, a decrease in depressive symptoms is coupled with a normalization of pro-inflammatory cytokines levels (Liu, Buisman-Pijlman, & Hutchinson, 2014). Animal studies have also shown that pro-inflammatory cytokines mediate depressive-like behaviors induced by stress, and administration of cytokine-inducer lipopolysaccharide (LPS) is sufficient to induce depressive-like behaviors (Fleshner, Frank, & Maier, 2017;Tang, Lin, Pan, Guan, & Li, 2016). The innate immune system senses pathogens through pattern recognition receptors (PRRs), and activation of PRRs induces downstream signaling pathways to mount appropriate immune responses (Liu & Ding, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Toll‐like receptor 4 on depressive‐like behaviors induced by chronic social defeat stress

et al. 2020

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Introduction A growing body of evidence suggests that stress is an important factor in depression, and pro‐inflammatory cytokines contribute to the occurrence and development of depression in both animal models and human patients. Toll‐like receptor 4 (TLR4) has been shown to be a key innate immune pattern recognition receptor involved in the regulation of stress responses and inflammation. However, the exact effects of TLR4 on depressive‐like behaviors induced by chronic social defeat stress (CSDS) are not known. Methods In this study, the effects of TLR4 on depressive‐like behaviors were investigated in an animal model of depression induced by CSDS. The depressive‐like behaviors were assessed by forced swimming test (FST), social interaction test (SIT), and light–dark box test (LDT). The protein expressions of TLR4 and tumor necrosis factor‐α (TNF‐α) in the hippocampus were measured using Western blotting. Results We found that CSDS increased TLR4 protein levels in the hippocampus and induced behavioral despair in FST, social avoidance in SIT, and anxiety‐like behavior in LDT. Fluoxetine normalized the increased expression of TLR4 and reversed behavioral despair, social avoidance, as well as anxiety‐like behavior induced by CSDS. However, directly blocking TLR4, by using either TLR4 inhibitor TAK‐242 or knockout of TLR4, only inhibited behavioral despair, but not social avoidance or anxiety‐like behavior induced by CSDS. Conclusions These results demonstrate a specific modulating role of TLR4 in behavioral despair induced by CSDS and suggest that TAK‐242 may be a beneficial treatment for patients with behavioral despair.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Toll‐like receptor 4 on depressive‐like behaviors induced by chronic social defeat stress

et al. 2020

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“…Researchers have reported that pro-inflammatory factors derived from activated microglia inhibit proliferation of NSCs and neurite outgrowth/branching. [39][40][41] In light of these findings, it is possible that the decreased neurogenesis and abnormal morphology of newborn neurons in the DG of cKO mice are attributable to pro-inflammatory factors released by activated microglia.…”

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confidence: 99%

Prenatal deletion ofDNA methyltransferase 1in neural stem cells impairs neurogenesis and causes anxiety-like behavior in adulthood

et al. 2016

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Despite recent advances in our understanding of epigenetic regulation of central nervous system development, little is known regarding the effects of epigenetic dysregulation on neurogenesis and brain function in adulthood. In the present study, we show that prenatal deletion of DNA methyltransferase 1 (Dnmt1) in neural stem cells results in impaired neurogenesis as well as increases in inflammatory features (e.g., elevated glial fibrillary acidic protein [GFAP] expression in astrocytes and increased numbers of microglia) in the adult mouse brain. Moreover, these mice exhibited anxiety-like behavior during an open-field test. These findings suggest that Dnmt1 plays a critical role in regulating neurogenesis and behavior in the developing brain and into adulthood.

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Leptin reduces LPS‐induced A1 reactive astrocyte activation and inflammation via inhibiting p38‐MAPK signaling pathway

Sun,

Song,

et al. 2024

Glia

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Neurotoxic A1 reactive astrocytes are induced by inflammatory stimuli. Leptin has been confirmed to have neuroprotective properties. However, its effect on the activation of A1 astrocytes in infectious inflammation is unclear. In the current study, astrocytes cultured from postnatal day 1 Sprague–Dawley rats were stimulated with lipopolysaccharide (LPS) to induce an acute in vitro inflammatory response. Leptin was applied 6 h later to observe its protective effects. The viability of the astrocytes was assessed. A1 astrocyte activation was determined by analyzing the gene expression of C3, H2‐D1, H2‐T23, and Serping 1 and secretion of pro‐inflammatory cytokines IL‐6 and TNF‐α. The levels of phospho‐p38 (pp38) and nuclear factor‐κB (NF‐κB) phosphor‐p65 (pp65) were measured to explore the possible signaling pathways. Additionally, an LPS‐induced inflammatory animal model was established to investigate the in vivo effects of leptin on A1 astrocytic activation. Results showed that in the in vitro culture system, LPS stimulation caused elevated expression of A1 astrocyte‐specific genes and the secretion of pro‐inflammatory cytokines, indicating the activation of A1 astrocytes. Leptin treatment significantly reversed the LPS induced upregulation in a dose‐dependent manner. Similarly, LPS upregulated pp38, NF‐κB pp65 protein and inflammatory cytokines were successfully reduced by leptin. In the LPS‐induced animal model, the amelioratory effect of leptin on A1 astrocyte activation and inflammation was further confirmed, showed by the reduced sickness behaviors, A1 astrocyte genesis and inflammatory cytokines in vivo. Our results demonstrate that leptin efficiently inhibits LPS‐induced neurotoxic activation of A1 astrocytes and neuroinflammation by suppressing p38‐MAPK signaling pathway.

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Hippocampal neurogenesis dysfunction linked to depressive-like behaviors in a neuroinflammation induced model of depression

Cited by 78 publications

References 47 publications

Effect of Toll‐like receptor 4 on depressive‐like behaviors induced by chronic social defeat stress

Effect of Toll‐like receptor 4 on depressive‐like behaviors induced by chronic social defeat stress

Prenatal deletion ofDNA methyltransferase 1in neural stem cells impairs neurogenesis and causes anxiety-like behavior in adulthood

Leptin reduces LPS‐induced A1 reactive astrocyte activation and inflammation via inhibiting p38‐MAPK signaling pathway

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