Brain inflammation is one of the main causes of epileptogenesis, a chronic process triggered by various insults, including genetic or acquired factors that enhance susceptibility to seizures. Amentoflavone, a naturally occurring biflavonoid compound that has anti-inflammatory effects, exerts neuroprotective effects against nervous system diseases. In the present study, we aimed to investigate the effects of amentoflavone on epilepsy in vivo and in vitro and elucidate the underlying mechanism. The chronic epilepsy model and BV2 microglial cellular inflammation model were established by pentylenetetrazole (PTZ) kindling or lipopolysaccharide (LPS) stimulation. Cognitive dysfunction was tested by Morris water maze while hippocampal neuronal apoptosis was evaluated by immunofluorescence staining. The levels of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome complexes and inflammatory cytokines were determined using quantitative real-time polymerase chain reaction, Western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay. Amentoflavone reduced seizure susceptibility, minimized PTZ-induced cognitive dysfunction, and blocked the apoptosis of hippocampal neurons in PTZ-induced kindling mice. Amentoflavone also inhibited the activation of the NLRP3 inflammasome and decreased the levels of inflammatory cytokines in the hippocampus of PTZ-induced kindling mice. Additionally, amentoflavone could alleviate the LPS-induced inflammatory response by inhibiting the NLRP3 inflammasome in LPS-induced BV2 microglial cells. Our results indicated that amentoflavone affects epileptogenesis and exerts neuroprotective effects by inhibiting the NLRP3 inflammasome and, thus, mediating the inflammatory process in PTZ-induced kindling mice and LPS-induced BV2 microglial cells. Therefore, amentoflavone may be a potential treatment option for epilepsy.

No abstract

ALG13 (asparagine-linked glycosylation 13) plays crucial roles in the process of N-linked glycosylation. Mutations of the ALG13 gene underlie congenital disorders of glycosylation type I (CDG-I), a rare human genetic disorder with defective glycosylation. Epilepsy is commonly observed in congenital disorders of glycosylation type I (CDG-I). In our study, we found that about 20% of adult ALG13KO knockout mice display spontaneous seizures, which were identified in a simultaneous video and intracranial EEG recording. However, the mechanisms of ALG13 by which deficiency leads to epilepsy are unknown. Whole-cell patch-clamp recordings demonstrated that ALG13KO mice show a marked decrease in gamma-aminobutyric acid A receptor (GABAAR)-mediated inhibitory synaptic transmission. Furthermore, treatment with low-dose diazepam (a positive allosteric modulator of GABAA receptors), which enhances GABAAR function, also markedly ameliorates severity of epileptic seizures in ALG13KO mice. Moreover, ALG13 may influenced the expression of GABAARα2 membrane and total protein by changing transcription level of GABAARα2. Furthermore, protein interactions between ALG13 and GABAARα2 were observed in the cortex of wild-type mice. Overall, these results reveal that ALG13 may be involved in the occurrence of epilepsy through the regulation of GABAAR function, and may provide new insight into epilepsy prevention and treatment.

Environmental cues associated with drug abuse are powerful mediators of drug craving and relapse in substance-abuse disorders. Consequently, attenuating the strength of cuedrug memories could reduce the number of factors that cause drug craving and relapse. Interestingly, impairing cue-drug memory reconsolidation is a generally accepted strategy aimed at reducing the intensity of cues that trigger drug-seeking and drug-taking behaviors. In addition, the agranular insular cortex (AI) is an important component of the neural circuits underlying drug-related memory reconsolidation. GABA B receptors (GABA B Rs) are potential targets for the treatment of addiction, and baclofen (BLF) is the only prototypical GABA B agonist available for application in clinical addiction treatment. Furthermore, DFosB is considered a biomarker for the evaluation of potential therapeutic interventions for addiction. Here, we used the morphine-induced conditioned place preference (CPP) paradigm to investigate whether postretrieval microinjections of BLF into the AI could affect reconsolidation of drug-reward memory, reinstatement of CPP, and the level of DFosB in mice. Our results showed that BLF infused into the AI immediately following morphine CPP memory retrieval, but not 6 h postretrieval or following nonretrieval, could eliminate the expression of a morphine CPP memory. This effect persisted in a morphine-priming-induced reinstatement test, suggesting that BLF in the AI was capable of preventing the reconsolidation of the morphine CPP memory. Our results also showed that the elimination of morphine CPP memory was associated with reduced morphine-associated DFosB expression in the longer term. Taken together, the results of our research provide evidence to support that GABA B Rs in the AI have an important role in drug-cue memory reconsolidation and further our understanding of the role of the AI in drug-related learning and memory.

<b><i>Background:</i></b> Long non-coding RNAs are reportedly endowed with the function of promoting or inhibiting cancer occurrence and development. The emphasis of this study was placed on the effect of lncRNA HLA complex group 11 (HCG11) on glioma progression, as well as its mechanism. <b><i>Methods:</i></b> Quantitative real-time polymerase chain reaction was utilized for detecting HCG11, miR-590-3p, and CAMD2 mRNA expression levels in glioma tissues. Western blot was adopted to examine cell adhesion molecule (CADM2) protein expression. Cell counting kit-8, BrdU, Transwell and wound healing assays were employed for investigating the malignant biological behaviors of glioma cells. RNA immunoprecipitation assay and dual-luciferase reporter assay were performed to prove the relationship between miR-590-3p and HCG11, as well as CADM2 and miR-590-3p. <b><i>Results:</i></b> HCG11 expression was lower in glioma tissues compared with that in paracancerous tissues, and its expression level was negatively correlated with WHO tumor stage. In addition, compared with in astrocyte cell line, the expression of HCG11 was lower in glioma cells. Functional experiments showed that HCG11 inhibited glioma cells migration and proliferation, while miR-590-3p facilitated these processes. Acting as a competitive endogenous RNA, HCG11 adsorbed miR-590-3p and upregulated the expression of CADM2, the target gene of miR-590-3p. <b><i>Conclusions:</i></b> HCG11 suppresses glioma cells proliferation and migration through regulating the miR-590-3p/CADM2 molecular axis.