Silencing MicroRNA-155 Attenuates Kainic Acid-Induced Seizure by Inhibiting Microglia Activation.

OBJECTIVE(S): Neuroinflammation is an important contributor to the development of seizures and epilepsy. Micro-RNA-155 (miR-155) plays a critical role in immunity and -inflammation. This study aims to explore the function of miR-155 and miR-155-mediated inflammation in epilepsy. METHODS: About 8-week-old male C57BL/6 mice were administered an intraperitoneal injection (i.p.) of kainic acid (KA) (15 mg/kg) or saline. The mice in the KA group developing acute seizure were further subjected to intracerebroventricular injection (i.c.v.) of antagomir negative control (NC) or miR-155 antagomir. Animal behavior was observed according to Racine's scale, and electroencephalographs were recorded. Primary microglia were cultured and treated with antagomir NC or antagomir. Whole-cell electrophysiological recording was conducted to detect the spontaneous EPSCs and IPSCs in the neurons treated with different conditioned medium from those microglia. miR-155 were detected by qRT-PCR in those models, as well as in the brain or blood from epileptic patients and healthy controls. RESULTS: miR-155 was abundantly expressed in glial cells compared with neurons, and its expression was markedly elevated in the brain of epilepsy patients and KA-induced seizure mice. Silencing miR-155 attenuated KA-induced seizure, abnormal electroencephalography, proinflammatory cytokine expression, and microglia morphology change. Moreover, conditioned media from KA-treated microglia impaired neuron excitability, whereas conditioned media from KA and miR-155 antagomir co-treated microglia had no such effects. Finally, miR-155 levels were significantly higher in the blood of epilepsy patients than those of healthy controls. CONCLUSION(S): These findings demonstrate that aberrant upregulation of miR-155 contributes to epileptogenesis through inducing microglia neuroinflammation.

Protective Role of L-3-n-Butylphthalide in Cognitive Function and Dysthymic Disorders in Mouse With Chronic Epilepsy.

Epilepsy is a common neurological disease with recurrent seizures and neurobehavioral comorbidities, including cognitive impairment and psychiatric disorders. Recent studies suggest that L-3-n-butylphthalide (NBP), an extract from the seeds of Apium graveolens Linn. (Chinese celery), ameliorates cognitive dysfunction in ischemia and/or Alzheimer's disease animal models. However, little is known about the role of NBP in epilepsy and the associated comorbidities. Here, using a pilocarpine-induced chronic epileptic mouse model, we found that NBP supplement not only alleviated seizure severity and abnormal electroencephalogram, but also rescued cognitive and emotional impairments in these epileptic mice. The possible underlying mechanisms may be associated with the protective role of NBP in reducing neuronal loss and in restoring the expression of neural synaptic proteins such as postsynaptic density protein 95 (PSD95) and glutamic acid decarboxylase 65/67 (GAD65/67). In addition, NBP treatment increased the transcription of neuroprotective factors, brain-derived neurotrophic factor and Klotho. These findings suggest that NBP treatment may be a potential strategy for ameliorating epileptogenesis and the comorbidities of cognitive and psychological impairments.

LncRNA Expression in CD4+ T Cells in Neurosyphilis Patients.

Recent studies have shown that several long noncoding RNAs (lncRNAs) are involved in regulating the immune response to cope with pathogenic invasion. To date, the roles of lncRNAs in the CD4+ T cell response to Treponema pallidum (T. pallidum) infection in neurosyphilis patients remain unknown. The mRNA and lncRNA expression profiles of CD4+ T cells that were isolated from neurosyphilis patients and healthy controls were analyzed by microarray. A total of 2258 lncRNAs and 1728 mRNAs were identified as over-expressed or under-expressed, respectively (fold change > 1.5) in the CD4+ T cells of neurosyphilis patients compared to the healthy controls. The lncRNA-mRNA co-expression network showed that 59 lncRNAs showed significant differences along with significantly different mRNAs. Among the 59 gene pairs, the LOC79999 mRNA was positively correlated with the RP11-160E2.16, RP11-160E2.11, and RP11-160E2.19 lncRNAs, and the NKX1-1 mRNA was positively correlated with the RP11-1398P2.1, RP11-160E2.19, and XLOC_003422 lncRNAs. The following five mRNAs were correlated with two differential lncRNAs: DUSP16, AP000349.1, FAM115C, TIMM8A, and SMCHD1. Gene Ontology (GO) analysis revealed that the differentially expressed coding genes were mainly involved in biological processes and the top 4 terms that associated with above-mentioned differentially expressed coding genes were as follows: defense response to fungus, defense response to bacterium, killing of cells of other organism and disruption of cells of another organism. A subsequent pathway analysis was also conducted, and several pathways, including the T cell receptor, MAPK, and TGF-beta signaling pathways, were associated with the differentially expressed mRNAs. This study reveals the differential expression profiles of lncRNAs in the CD4+ T cell response to the T. pallidum infection in neurosyphilis patients. LncRNAs are involved in key biological processes that comprise the CD4+ T cell response to the T. pallidum infection.