Long-term potentiation-based screening identifies neuronal PYGM as a synaptic plasticity regulator participating in Alzheimer's disease

Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,with impaired LTP found to be associated with AD.However,the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated.Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear.Herein,we induced LTP in the hippocampal CA1 region of wildtype(WT)and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region.We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes(DEGs)in mice with normal LTP,and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP.We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction.Among them,we found that the expression of Pygm,which catabolizes glycogen,was also decreased in AD patients.We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice,while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice.Moreover,we showed that PYGM directly regulated energy generation in neurons.Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function,but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.

PYGM基因SNP及单体型多态性与女子长跑运动员生理表型的关联性

目的:探讨PYGM基因SNP及单体型多态性与女子长跑运动员生理表型的关联性。方法:研究对象为我国备战2012年伦敦奥运会国家集训队的79名女子长跑运动员。对PYGM基因的rs483962、rs490980和rs589691 3个位点进行基因型和单体型分析;并研究基因型和单体型与各生理表型指标的关联性。结果:1)rs490980位点不同基因型与运动员VO2AT/W显著相关(P<0.05),CC型显著性低于TT型和TC型;rs589691位点不同基因型与运动员WHR显著相关,CC型显著性低于TC型和TT型;2)由rs490980-rs589691位点组成的单体型与WHR显著性相关,TT单体型携带者WHR显著性高于非TT单体型携带者。结论:1)PYGM基因rs490980位点可以作为与有氧运动能力表型有关联性的基因标记;2)PYGM基因rs589691位点和rs490980-rs589691位点组成的单体型可以作为与身体成分有关联性的基因标记。

秦川牛PYGM基因的表达及其遗传变异对胴体和体尺性状的影响

【目的】以秦川牛糖原磷酸化酶基因PYGM为候选基因，研究其在秦川牛生长和胴体性状形成中的作用。【方法】以300头（24±2）月龄纯种秦川牛为试验材料，通过DNA测序和PCR—RFLP技术，研究PYGM基因的多态性对秦川牛个体宰前活体质量、胴体质量、体高、体斜长和屠宰率共5个性状的影响；运用RT—PCR技术分析PyGM基因在秦川牛成体和4～5月龄胎牛2个阶段的肺脏、心脏、肝脏、舌、背最长肌及脾脏6种组织中的表达情况。【结果】半定量RT—PCR检测结果显示，PYGM基因在秦川牛胎儿和成年时期的心脏、舌及背最长肌组织中的表达量均显著高于其他组织。并在该基因中筛查到了2个新的单核苷酸变异（sNP）位点，分别为PYGM内含子1上的c—T突变和内含子6中的c—G突变。群体多态性分析结果表明，秦川牛群体在这2个位点处于Hardy-Weinberg平衡状态，并且处于中度多态。2个SNP位点中A和c等位基因为优势等位基因，SNP1位点上AA和AB基因型个体的宰前活体质量和胴体质量显著高于纯合的BB基因型个体；SNP2位点上CC基因型个体的体高显著高于DD基因型个体。【结论1PYGM基因可以作为秦川牛品种改良中与肌肉生长相关的候选基因。

一例PYGM基因复合杂合突变导致糖原累积症Ⅴ型的诊断和基因检测分析

糖原累积症Ⅴ型是一种由肌糖原磷酸化酶(muscle glycogen phosphorylase,PYGM)缺陷引起的常染色体隐性遗传疾病,其临床特征为运动不耐受、再振作现象和血清肌酸激酶水平增高。本文报道了1例中国糖原累积症Ⅴ型年轻男性患者,运动后双下肢无力、血肌酸激酶升高、肌肉磁共振可见下肢近端后群肌轻度脂肪浸润,基因检测结果显示先证者具有复合杂合型PYGM致病突变,分别为来自母亲的c.308T>C (p.L103P)变异和来自父亲的c.260_261delCT (p.S87Ffs*23)变异,其中前者为新发突变。本研究丰富了PYGM致病基因突变谱,有助于提高临床医生对糖原累积症Ⅴ型的认识,并为该疾病的进一步遗传学研究提供参考。

猪肌肉糖原磷酸化酶基因的多态性及其与胴体和肉质性状的相关分析

试验旨在寻找不同品种猪的差异表达基因,并对其遗传效应进行初步分析。应用抑制消减杂交技术获得了在梅山猪、长白猪和大白猪中差异表达的肌肉糖原磷酸化酶(glycogen phosphorylase,muscle form,PYGM)基因及其全长cDNA序列,序列分析结果表明,猪PYGM基因编码842个氨基酸,与人、牛、狗、小鼠、大鼠和羊的氨基酸序列具有96%、97%、96%、96%、96%和97%的相似性,而且该基因在各组织中表达量均很高。通过序列比对发现,在3′非翻译区(3′UTR)125 bp处存在1个突变。利用PCR-RFLP方法,在大白猪、梅山猪、长白纯种猪和170头大白×梅山F2代资源家系中检测了该突变位点的多态性并进行性状关联分析,结果表明,该位点的多态性与瘦肉率、骨率、肥肉率、平均背膘厚、眼肌面积、胴体长显著相关,尤其是活体瘦肉率AA基因型(大白猪、长白猪优势基因)比BB基因型(梅山猪优势基因)高3%,肥肉率低5%,与外来猪种瘦肉率显著高于本地猪的性状表现是一致的。因此,猪PYGM基因125 bp位点可能是一个潜在的分子标记辅助常规育种位点。