Dynorphin/KOR inhibits neuronal autophagy by activating mTOR signaling pathway to prevent acute seizure epilepsy.

In previous studies, we found that dynorphin exerts antiepileptic effect by activating the kappa opioid receptor (KOR). However, the role of neuronal autophagy in dynorphin/KOR-mediated antiepileptic is still unclear. This study aimed to investigate the molecular mechanism of dynorphin's antiepileptic effect by inhibiting autophagy and reducing neuronal apoptosis. Here, a pilocarpine-induced rat model of epilepsy was established and hippocampal neurons were treated with Mg2+ -free exposed for epileptiform activity induction. The real-time polymerase chain reaction and Western blot analysis were used to evaluate messenger RNA and protein expression. The TdT-mediated dUTP-biotin nick end labeling staining and flow cytometry were used to analyze cell apoptosis in vivo and in vitro. Neuron cells viability was detected by Cell Counting Kit-8 assay. Immunofluorescent staining and green fluorescent protein-light chain 3 immunofluorescence were used to measure autophagy in vivo and in vitro. Results showed that overexpression of prodynorphin alleviated neuronal apoptosis, activated the mammalian target of rapamycin (mTOR) signaling pathway, and inhibited neuronal autophagy in epileptic rats. Dynorphin inhibited Mg2+ -free-induced seizure-like neuron apoptosis, partially reversing the effect of Mg2+ -free on the mTOR signaling pathway and seizure-like neuron autophagy. Further, using rapamycin, we found that dynorphin inhibited Mg2+ -free-induced seizure-like neuron autophagy and apoptosis by activating the mTOR signaling pathway. In conclusion, dynorphin inhibits autophagy by activating the mTOR signaling pathway and has a protective effect on epilepsy acute seizure and epilepsy-induced brain injury.

[Allergens and their relationships to childhood bronchial asthma in the Jiading District of Shanghai].

OBJECTIVE: To study allergens and their relationship to the occurrence of childhood bronchial asthma in the Jiading District of Shanghai. METHODS: Three hundred and eighty-two 4 to 12-year-old children with asthma in the remission stage from Nanxiang Hospital in the Jiading District of Shanghai were used as a case group (asthma group), and 402 children from two primary schools and two kindergartens in Jiading were enrolled by cluster sampling and served as control group. Parents of the children completed a questionnaire on living conditions and allergy-related disease history. Skin prick test (SPT) for 18 common allergens was carried out in both groups. In order to examine the effect of environment and living conditions on SPT results, children in the control group were further divided into two sub-groups according to birth place: migrant (219 cases) and resident (183 cases). RESULTS: SPT results revealed that the main allergens identified in the Jiading region were dermatophagoides farinae, house dust mites, shrimps, cockroaches, and dog hair. The SPT positive rate was 67.9% in the asthma group, and this was significantly higher than in the control group (31.8%) (P<0.01). The environment and living conditions in the migrant group were significantly different from the resident group (P<0.01), whereas the SPT positive rate for this group was significantly lower than in the resident group (P<0.01). CONCLUSIONS: Allergens in the Jiading region mainly originate from dermatophagoides farinae, household dust mites, shrimps, cockroaches and dog hair. Children with asthma are more susceptible to allergens. Environment and living conditions may be relevant, to a certain extent, to an SPT positive rate.