Identification of autosomal dominant lateral temporal epilepsy caused by a novel mutation in RELN in China: a case report

Background Temporal lobe epilepsy is the most common type of focal epilepsy,but hereditary factors are usually overlooked.Reelin(RELN)is considered to be the second most common pathogenic gene implicated in autosomal dominant lateral temporal epilepsy(ADLTE).However,this mutation is not frequently discovered in the Chinese population.Additionally,there are few clinical studies regarding the connection between RELN and glioma.Case presentation The healthcare records of an 8-year-old child who experienced generalized tonic-clonic seizures(GTCS)during sleep for 7 years were retrospectively analyzed.In addition to experiencing his first seizure at the age of one,his mother also suffered from GTCS during her pregnancy,and a glioma was discovered.An investigation involving gene sequencing was conducted on the proband and his parents.He was diagnosed with ADLTE once a missense mutation in RELN(c.1799 C>T)was identified as the causal factor.The mutation was inherited from his mother.He was taking levetiracetam(500 mg twice a day)to avoid seizures,but his mother died of status epilepticus caused by glioma recurrence two years earlier.Conclusions Genetic issues should be given more consideration in cases of temporal lobe epilepsy.If the source of the seizures is determined to be inherited,anti-seizure medications should be used for prolonged periods.Furthermore,more research is required to determine whether mutations in RELN are related to the occurrence and progression of gliomas.

Amyloid-β depresses excitatory cholinergic synaptic transmission in Drosophila

Objective Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer＇s disease （AD）. Although amyloid-β （Aβ） aggregation is a pathological hallmark of AD, the mechanisms by which Aβ peptides modulate cholinergic synaptic transmission and memory loss remain obscure. This study was aimed to investigate the potential synaptic modulation by Aβ of the cholinergic synapses between olfactory receptor neurons and projection neurons （PNs） in the olfactory lobe of the fruit fly. Methods Cholinergic spontaneous and miniature excitatory postsynaptic current （mEPSC） were recorded with whole-cell patch clamp from PNs in Drosophila AD models expressing Aβ40, Aβ42, or Aβ42Arc peptides in neural tissue. Results In fly pupae （2 days before eclosion）, overexpression of Aβ42 or Aβ42Arc, but not Aβ40, led to a significant decrease of mEPSC frequency, while overexpression of Aβ40, Aβ42, or Aβ42Arc had no significant effect on mEPSC amplitude. In contrast, Pavlovian olfactory associative learning and lifespan assays showed that both short-term memory and lifespan were decreased in the Drosophila models expressing Aβ40, Aβ42, or Aβ42Arc. Conclusion Both electrophysiological and behavioral results showed an effect of Aβ peptide on cholinergic synaptic transmission and suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.

HHLA2过表达胃癌细胞株构建及细胞功能的初步研究

目的使用慢病毒载体构建稳定过表达人内源性逆转录病毒H-长末端重复关联蛋白2(HHLA2)的胃癌细胞系,探讨细胞发生的生物学功能改变。方法由目的基因以及Lipo2000转染试剂构建重组质粒,将该质粒转染293T细胞,浓缩其细胞上清液并测定浓度,再将浓缩液转染胃癌细胞株BGC-823和MGC80-3,利用流式细胞术分选并验证GFP+稳定过表达的细胞株。开展细胞功能实验(含迁移试验和增殖试验等)以分析过表达HHLA2胃癌细胞株的生物学功能。结果酶切及测序结果示,重组慢病毒载体成功构建。流式分选及验证示,HHLA2过表达胃癌稳转株。过表达HHLA2可使胃癌细胞株MGC80-3和BGC-823加快增殖,其24 h、48 h、72 h吸光度值均较对照细胞株升高(P<0.05)。过表达HHLA2可增强胃癌细胞株BGC-823的迁移能力,其24 h、48 h迁移率均较对照细胞株升高(P<0.05);MGC80-3细胞迁移距离未明显变长(P>0.05)。结论HHLA2过表达能够提高胃癌细胞的增殖和迁移能力。