Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the α7 nicotinic acetylcholine receptor

Li, Xiaolan; Han, Xinjia; Bao, Junjie; Liu, Yuanyuan; Ye, Aihua; Thakur, Mukesh; Liu, Huishu

doi:10.1016/j.brainres.2016.04.043

Cited by 27 publications

(23 citation statements)

References 43 publications

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“…Increasing evidence has shown that activated microglia could secret proinflammatory cytokines as well as reduce the seizure threshold. In this manner, microglia might help generate seizures via releasing and responding to endogenous inflammatory mediators including IL-1β, TNF-α and IL-6 [18,19]. While it is unclear how epilepsy augments inflammasome activation, in this study we found abnormal circRNA expression relative to the microglial phenotype.…”

Section: Discussionmentioning

confidence: 48%

The mmu_circ_0000335 inhibits M1 microglial-induced hippocampal neuronal apoptosis via the miR-19b-3p/SOCS1 axis in a mouse epilepsy model

Zhu

Kuang

et al. 2019

Preprint

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Background : Increasing evidence has demonstrated that circular RNAs (circRNAs) participate in epileptogenesis, but the expression profile and role of circRNAs in epilepsy remain unknown. A circRNA microarray was performed to examine epilepsy-related circRNAs. Bioinformatics analyses, luciferin reporter experiments and real-time quantitative PCR (Rt-qPCR) in vitro experiments were performed to demonstrate the mechanism of circRNA-mediated gene regulation of the microglial phenotype under epileptic conditions. Then, to further confirm the effect of circRNAs on nerve damage in the hippocampus, a mouse model of epilepsy was established by intraperitoneal injection of lithium chloride and pilocarpine. Results: The data indicated that 364 circRNAs were differentially expressed comparing epilepsy and control tissues. In particular, mmu_circ_0000335 expression was significantly downregulated in epileptic mice which was confirmed by Rt-qPCR. Overexpression of mmu_circ_0000335 promoted BV2 cell transformation into the M2 macrophage phenotype by increasing expression of CD206, Arg1, Ym1 and IL-10 while decreasing M1 macrophage markers IL-1β, IL-6, TNF-α and IFN-γ expressions under epileptic conditions. mmu_circ_0000335 expression triggered upregulation of Suppressor of Cytokine Signaling 1 (SOCS1) by decreasing miR-19b-3p levels, as determined by luciferase reporter assay. In vivo studies found that mmu_circ_0000335 overexpression decreased epilepsy-induced neural cell apoptosis in the hippocampus by reducing inflammatory cytokine expression. Immunofluorescence detection showed that mmu_circ_0000335 overexpression promoted microglial transformation into the M2 phenotype which had an anti-inflammatory effect. Conclusions: These results collectively indicated that mmu_circ_0000335 was involved in epilepsy progression by functioning as a miR-19b-3p sponge to enhance SOCS1 expression. Thus, mmu_circ_0000335 may be a candidate therapeutic target for epilepsy patients.

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Section: Discussionmentioning

confidence: 48%

The mmu_circ_0000335 inhibits M1 microglial-induced hippocampal neuronal apoptosis via the miR-19b-3p/SOCS1 axis in a mouse epilepsy model

Zhu

Kuang

et al. 2019

Preprint

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“…The presence of maternal hypertension and albuminuria demonstrated that the PE and E models are successful. After PTZ injection, we found that the latency to seizure in the PE + PTZ group (73.2 ± 6.6 s) was significantly less than that of the P + PTZ (107.0 ± 7.4 s) or NP + PTZ (122.5 ± 10.4 s) groups; the number of surviving neurons in the CA1 area in the P + PTZ (67.44 ± 5.598/mm 2 ) group was significantly lower compared with those in the NP (85.9 ± 78.224/mm 2 ) and P (87.42 ± 12.912/mm 2 ) groups; that number in the PE + PTZ (57.92 ± 5.91/mm 2 ) group also decreased significantly compared with the P + PTZ group [ 23 ]. These results suggested that compared with the non-pregnant rats and pregnant rats, it was much easier to induce seizures and neuronal damage in the pre-eclamptic rats.…”

Section: Resultsmentioning

confidence: 99%

Changes in the Expression of AQP4 and AQP9 in the Hippocampus Following Eclampsia-Like Seizure

Han

Huang

Liu

et al. 2018

IJMS

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Eclampsia is a hypertensive disorder of pregnancy that is defined by the new onset of grand mal seizures on the basis of pre-eclampsia. Until now, the mechanisms underlying eclampsia were poorly understood. Brain edema is considered a leading cause of eclamptic seizures; aquaporins (AQP4 and AQP9), the glial water channel proteins mainly expressed in the nervous system, play an important role in brain edema. We studied AQP4 and AQP9 expression in the hippocampus of pre-eclamptic and eclamptic rats in order to explore the molecular mechanisms involved in brain edema. Using our previous animal models, we found several neuronal deaths in the hippocampal CA1 and CA3 regions after pre-eclampsia and that eclampsia induced more neuronal deaths in both areas by Nissl staining. In the current study, RT-PCR and Western blotting data showed significant upregulation of AQP4 and AQP9 mRNA and protein levels after eclamptic seizures in comparison to pre-eclampsia and at the same time AQP4 and AQP9 immunoreactivity also increased after eclampsia. These findings showed that eclamptic seizures induced cell death and that upregulation of AQP4 and AQP9 may play an important role in this pathophysiological process.

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“…Endogenous ligands of TLR4, including IL-1β, may be generated by microglia following brain injury, mimicking the effect of LPS ( 29 ). An animal study indicated that activated microglia release proinflammatory molecules to decrease the seizure threshold ( 30 ). Consequently, microglia may help generate seizures by releasing, and responding to, endogenous inflammatory mediators, including IL-1β and TNF-α ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of ganoderic acid A on lipopolysaccharide‑induced proinflammatory cytokine release from primary mouse microglia cultures

Chi

Wang

et al. 2017

Exp Ther Med

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For several thousand years, Ganoderma lucidum (Ling-Zhi in Chinese and Reishi in Japanese) has been widely used as a traditional medication for the prevention and treatment of various diseases in Asia. Its major biologically active components, ganoderic acids (GAs), exhibit significant medicinal value due to their anti-inflammatory effects. Dysregulation of microglial function may cause seizures or promote epileptogenesis through release of proinflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. At present, only little information is available on the effects of GAs on microglia-mediated inflammation in vitro and/or in vivo. The present study aimed to investigate the role of GA-A on microglia-mediated inflammation in vitro. In addition, the effect of GA-A on lipopolysaccharide (LPS)-evoked alterations in mitochondrial metabolic activity of microglia was evaluated. The results of the present study demonstrated that GA-A significantly decreased LPS-induced IL-1β, IL-6 and TNF-α release from mouse-derived primary cortical microglial cells in a concentration-dependent manner. GA-A treatment reduced LPS-induced expression of nuclear factor (NF)-κB (p65) and its inhibitor, demonstrating that non-toxic suppression of IL-1β, IL-6 and TNF-α production by GA-A is, at least in part, due to suppression of the NF-κB signaling pathway. In addition, the LPS-induced stimulation of mitochondrial activity of microglial cells was abolished by co-treatment with GA-A. Thus, GA-A treatment may be a potential therapeutic strategy for epilepsy prevention by suppressing microglia-derived proinflammatory mediators.

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Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the α7 nicotinic acetylcholine receptor

Cited by 27 publications

References 43 publications

The mmu_circ_0000335 inhibits M1 microglial-induced hippocampal neuronal apoptosis via the miR-19b-3p/SOCS1 axis in a mouse epilepsy model

The mmu_circ_0000335 inhibits M1 microglial-induced hippocampal neuronal apoptosis via the miR-19b-3p/SOCS1 axis in a mouse epilepsy model

Changes in the Expression of AQP4 and AQP9 in the Hippocampus Following Eclampsia-Like Seizure

Effects of ganoderic acid A on lipopolysaccharide‑induced proinflammatory cytokine release from primary mouse microglia cultures

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