Gestational valproic acid exposure enhances facial stimulation-evoked cerebellar mossy fiber-granule cell transmission via GluN2A subunit-containing NMDA receptor in offspring mice.

Valproic acid (VPA) is one of the most effective antiepileptic drugs, and exposing animals to VPA during gestation has been used as a model for autism spectrum disorder (ASD). Numerous studies have shown that impaired synaptic transmission in the cerebellar cortical circuits is one of the reasons for the social deficits and repetitive behavior seen in ASD. In this study, we investigated the effect of VPA exposure during pregnancy on tactile stimulation-evoked cerebellar mossy fiber-granule cell (MF-GC) synaptic transmission in mice anesthetized with urethane. Three-chamber testing showed that mice exposed to VPA mice exhibited a significant reduction in social interaction compared with the control group. In vivo electrophysiological recordings revealed that a pair of air-puff stimulation on ipsilateral whisker pad evoked MF-GC synaptic transmission, N1, and N2. The evoked MF-GC synaptic responses in VPA-exposed mice exhibited a significant increase in the area under the curve (AUC) of N1 and the amplitude and AUC of N2 compared with untreated mice. Cerebellar surface application of the selective N-methyl-D-aspartate (NMDA) receptor blocker D-APV significantly inhibited facial stimulation-evoked MF-GC synaptic transmission. In the presence of D-APV, there were no significant differences between the AUC of N1 and the amplitude and AUC of N2 in the VPA-exposed mice and those of the untreated mice. Notably, blockade of the GluN2A subunit-containing, but not the GluN2B subunit-containing, NMDA receptor, significantly inhibited MF-GC synaptic transmission and decreased the AUC of N1 and the amplitude and AUC of N2 in VPA-exposed mice to levels similar to those seen in untreated mice. In addition, the GluN2A subunit-containing NMDA receptor was expressed at higher levels in the GC layer of VPA-treated mice than in control mice. These results indicate that gestational VPA exposure in mice produces ASD-like behaviors, accompanied by increased cerebellar MF-GC synaptic transmission and an increase in GluN2A subunit-containing NMDA receptor expression in the offspring.

LncRNA FTX inhibits hippocampal neuron apoptosis by regulating miR-21-5p/SOX7 axis in a rat model of temporal lobe epilepsy.

Emerging evidence has shown that long noncoding RNA (LncRNA) is involved in the development of epileptogenesis. However, the expression profile and the biological function of FTX in epilepsy remains unclear. This study aimed to provide functional evidence and elucidate the molecular mechanisms by which the FTX affects status epilepticus (SE) induced hippocampal apoptosis. SE rat model was introduced by intraperitoneal injection of lithium chloride and pilocarpine. Our results showed that FTX is notably reduced in the hippocampus. Moreover, the in vivo overexpression of FTX inhibited SE-induced hippocampus neuron apoptosis. Mechanically, we found that FTX negatively regulated miR-21-5p expression by targeting its 3'UTR to regulate neuron apoptosis. Upregulation of miR-21-5p attenuates anti-apoptosis property of FTX overexpression by regulating SOX7 expression in epileptiform hippocampal neurons. Collectively, our study for the first time demonstrated the anti-apoptosis ability of FTX during epileptogenesis and uncovered a novel FTX-mediated mechanism in SE-induced neural apoptosis by targeting miR-21-5p/SOX7 axis, which provides a new target in developing lncRNA-based strategies to reduce SE-induced hippocampal neuron apoptosis.