Inhibition of neuronal pentraxin 2 relieved epileptic seizure via reducing GluA1 phosphorylation.

Neuronal pentraxin 2 (Nptx2), a member of the synaptic protein family linked to excitatory synaptic formation, is found to be upregulated in epileptic mice, yet its role in epilepsy has been unclear. In vivo, we constructed a mouse model of epilepsy by using kainic acid induction. In vitro experiments, a Mg2+-free medium was used to induce epileptiform discharges in neurons. The results showed that the Nptx2 was upregulated in epileptic mice. Moreover, Nptx2 knockdown reduced the number of seizures and seizure duration. Knocking down Nptx2 not only reduced the number and duration of seizures but also showed a decrease in electroencephalogram amplitude. Behavioral tests indicated improvements in learning and memory abilities after Nptx2 knockdown. The Nissl staining and Timms staining revealed that Nptx2 silencing mitigated epilepsy-induced brain damage. The immunofluorescence staining revealed that Nptx2 absence resulted in a reduction of apoptosis. Nptx2 knockdown reduced Bax, cleaved caspase3, and cleaved caspase9 expression, while increased Bcl-2 expression. Notably, Nptx2 knockdown inhibited GluA1 phosphorylation at the S831 site and reduced the GluA1 membrane expression. The PSD95 expression declined in the epilepsy model, while the Nptx2 knockdown reversed it. Collectively, our study indicated that Nptx2 silencing not only alleviated brain damage and neuron apoptosis but also improved learning and memory ability in epileptic mice, suggesting Nptx2 as a promising target for epilepsy treatment.

Long noncoding RNA MEG8 induces an imbalance of Th17/Treg cells through the miR-107/STAT3 axis in Henoch-Schonlein purpura rats.

T-helper (Th) 17/ T-regulatory (Treg) cell dysregulation underlies the pathogenesis of Henoch-Schonlein purpura (HSP). This research focused on the implication/s of the long noncoding RNA (lncRNAs) maternally expressed gene 8 (MEG8) in Th17 and Treg cell differentiation in HSP rats. MEG8, miR-107, signal transducer and activator of transcription-3 (STAT3), receptor-related orphan receptor γt (RORγt), and the transcription factor forkhead box P3 (Foxp3) expression levels were detected using real-time quantitative polymerase chain reaction and Western blot analyses. Flow cytometry was employed for measuring Th17 and Treg cells within the CD4+ T cell population. The interaction between miR-107 and MEG8 or STAT3 was examined. A low proportion of MEG8 and Treg cells together with Th17 cells were denoted within HSP rats. Moreover, MEG8 overexpression altered the Th17/Treg imbalance in peripheral blood CD4+ T-cell population, and the miR-107 mimic and STAT3 silencing reversed this effect. Thus, MEG8 served as a sponge for miR-107, lowering binding activity to STAT3 and thus overexpressing the molecule. Taken together, MEG8 induces an imbalance of Th17/Treg cells through the miR-107/STAT3 axis in HSP rats.