Objective To investigate the effects of hippocampal neurons autophagy and endoplasmic reticulum stress(ERS) on the memory function of mice after focal cerebral ischemia-reperfusion(I-R), and the possible mechanism of ...
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Objective To investigate the effects of hippocampal neurons autophagy and endoplasmic reticulum stress(ERS) on the memory function of mice after focal cerebral ischemia-reperfusion(I-R), and the possible mechanism of cerebral-protective effects by 4-BPA. Methods Totally 120 male adult C57BL/6 mice were divided in to 3 groups randomly:(1) sham group,(2) I/R group,(3) I/R+ 4-PBA group. The mice from sham group received only sham surgery. Mice in both I/R group and I/R+ 4-PBA group received 90-minute of middle cerebral artery occlusion(MCAO). The mice in I/R+ 4-PBA group were treated by intraperitoneal injection of 4-PBA(120mg/kg) i.p. immediately after MCAO, once a day for 3 days. Ended the mice and prepared brain tissue samples at 6h, 12 h, 24 h, 48 h and 72 h after I/R, 6 mice included each time. Measured the infarct size using Triphenyte-trazoliumchloride(TTC) method, observed the morphological changes by H.E. staining, evaluated the location and expression level of glucose regulated protein(GRP78), HSP70 and LC3 in hippocampus by immunochemistry and Western blot respectively, detected the co-location of LC3 and HSP70 by double immunofluorescent staining, assessed the neural function by neurological impairment score(full points, 24) at 24 h, 48 h and 72 h after I/R and tested the spatial memory ability of another 30 mice at Day 7-10 after I/R by Morris Water Maze(MWM). Results No distinct pathological changes in sham group. Obvious infarct lesions appeared in I/R group, neurons arrange disorderly, show swelling, vacuoles and partial karyopyknosis in hippocampal CA1 area. GRP78, HSP70 and LC3 began to increase at 6h after I/R, the expression maximum of them were at 12 h, 24 h and 24 h respectively, then gradually declined. The expression of GRP78, HSP70 and LC3 presented the same expressional tendencies found in I/R+ 4-BPA group, with remarkably decreased expression level compared to I/R group but still higher expression level compared to sham group. Double immunofl
Congenital hypomyelinating leukodystrophies(HLDs) is a spectrum of genetic disorders with deficiency of myelin substantial deposit in brain white matter, causing development delay, nystagmus and/or other manifestation...
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Congenital hypomyelinating leukodystrophies(HLDs) is a spectrum of genetic disorders with deficiency of myelin substantial deposit in brain white matter, causing development delay, nystagmus and/or other manifestations. The brain MRI will show hypomyelination change. Until now more than 10 disorders has been recognized in HLDs, in which Pelizaeus-Merzbacher disease(PMD) accounts for the most. Objective To analyze the clinical and genetic characteristics of Chinese HLD patients. Method Patients with developmental delay and hypomyelinating change in brain MRI in our clinic from Sep, 2005 to Nov, 2014 are collected. Clinical analysis includes symptoms, physical examinations, brain MRIs and other laboratory examinations;Genetic analysis consists NGS(next generation sequencing), which includes all genes underlying congenital hypomyelinating leukodystrophies. MLPA(multiplex ligation probe amplication) technique was used to detect possible PLP1 duplication mutation. All pathological mutations have been confirmed by Sanger sequencing or MLPA. Result 124 patients have been diagnosed HLDs clinically, including 95 PMD(95/124, 76.61%), 12 PMLD(Pelizaeus-Merzbacher-like disease, 12/124, 9.68%), 7 GM1/GM2 gangliosidosis(7/124, 5.64%), and other rare diseases such as H-ABC, Sjogren-Larsson syndrome, SPG-35, trichothiodystrophy, MSUD(Maple syrup urine disease), NCL(Neuronal Ceroid Lipofuscinosis) and 18 q deletion syndrome. Development delay and nystagmus are among the most often seen symptoms, while clinical examinations and brain MRI have provided important help for diagnosis. Among them 113 patients are found gene mutation or chromosome change. Meanwhile, molecular diagnosis of left patients are unknown(11/124, 8.87%). The genes with mutations include PLP1(89/113, 78.76%), GJC2(9/113, 7.96%), GLB1(5/113, 4.42%), HEXA(2/113, 1.77%), TUBB4A(2, 1.77%), and ALDH3A2, POLR3A, FA2H, ERCC2,BCKDHB. One chromosome 18 q terminal deletion has also been found. Conclusion PMD caused by PLP1 m
目的:孤独谱系障碍(Autism Spectrum Disorder,ASD)是一种严重的神经发育障碍性疾病,d目前病因尚不明确,一般起病于儿童早期,临床主要表现为社会交流障碍、兴趣狭窄或重复刻板行为。众多研究提示ASD患儿的脑灰质体积存在异常,并与临床症状相关,横断面研究结论常不一致,需要在纵向研究中进一步探索。本研究以2～3岁的ASD儿童和发育迟缓(Developmental Delay,DD)儿童为研究对象,纵向对比分析两组儿童脑灰质结构的发育轨迹,并结合神经心理评估结果,研究ASD儿童脑灰质的异常发育和临床症状及严重程度的相关性。方法:对37名符合美国精神障碍诊断和统计手册第四版(修订版)(The Diagnostic and Statistical Manual of Mental Disorders,Fouth Text Revision,DSM-Ⅳ-TR)诊断标准的ASD儿童和27例年龄、性别及发育商匹配的DD儿童分别在2～3岁及4～5岁时均采用T1-weight加权序列进行头部磁共振成像(Magnetic Resonance Imaging,MRI)扫描。使用基于体素的形态学测量(Voxel Based Morphometry,VBM)技术研究ASD儿童大脑灰质及各亚区结构灰质体积随时间的变化程度。同时结合儿童孤独症评定量表(Childhood Autism Rating Scale,CARS)评估两组儿童的临床症状,分析ASD临床症状严重程度变化与脑灰质结构体积变化之间的相关性。结果:(1)2～3岁时,ASD组儿童全脑体积、全脑灰质体积均显著大于对照组(P<0.05)。进一步分析脑叶,ASD组儿童双侧大脑、额叶及颞叶的灰质体积均显著大于对照组(P<0.05),其余脑叶的灰质体积两组间均无显著差异(P>0.05)。以年龄为协变量进行协方差分析时,两组儿童全脑体积、全脑灰质体积均无显著差异(P>0.05)。进一步分析脑叶,ASD组儿童双侧颞叶灰质体积仍显著大于对照组(P<0.05),其余脑叶的灰质体积两组间均无显著差异(P>0.05)。以全脑体积为协变量进行协方差分析时,两组儿童的全脑灰质体积无显著差异(P>0.05)。进一步分析脑叶,ASD组儿童的双侧顶叶灰质体积显著大于对照组(P<0.05),其余脑叶的灰质体积两组间均无显著差异(P>0.05)。(2)2～3岁时,ASD组儿童的左侧背外侧额上回、左侧眶部额上回、双侧额中回、左侧补充运动区、双侧内侧额上回、双侧眶内额上回、双侧回直肌、双侧脑岛、双侧前扣带和旁扣带脑回、双侧杏仁核、左侧枕中回、左侧枕下回、双侧尾状核、右侧豆状壳核、双侧豆状苍白球、双侧颞极:颞上回、左侧颞中回、双侧左侧颞极:颞中回、右侧颞下回的灰质体积均显著大于对照组(P<0.05),其余区域的灰质体积两组间均无显著差异(P>0.05)。以年龄为协变量进行协方差分析时,ASD组儿童的双侧内侧额上回、双侧眶内额上回、双侧回直肌、双侧脑岛、双侧杏仁核、左侧枕下回、双侧尾状核、左侧豆状苍白球、左侧颞极:颞上回、双侧颞极:颞中回的灰质体积仍显著大于对照组(P<0.05),其余区域的灰质体积两组间均无显著差异(P>0.05)。以全脑体积为协变量进行协方差分析时,ASD组儿童的右侧中央沟盖、右侧眶内额上回、左侧杏仁核、右侧距状裂周围皮层、右侧舌回、右侧顶上回、左侧楔前叶、左侧颞极:颞中回的灰质体积均显著大于对照组(P<0.05),其余区域的灰质体积两组间均无显著差异(P>0.05)。(3)4～5岁时,ASD组儿童全脑体积、全脑灰质体积均显著大于对照组(P<0.05)。进一步分析脑叶,ASD组儿童的双侧大脑、额叶及颞叶的灰质体积均显著大于对照组(P<0.05),其余脑叶的灰质体积两组间均无显著差异(P>0.05)。以年龄为协变量进行协方差分析时,两组儿童的全脑体积、全脑灰质体积显著性差异仍然存在(P<0.05)。进一步分析脑叶,ASD组儿童双侧大脑、额叶及颞叶的灰质体积仍显著大于对照组(P<0.05),其余脑叶的灰质体积两组间均无显著差异(P>0.05)。以全脑体积为协变量进行协方差分析后,ASD组儿童的左侧顶叶、右侧枕叶灰质体积均显著大于对照组(P<0.05),其余脑叶的灰质体积均无显著差异(P>0.05)。(4)4～5岁时,ASD组儿童的双侧中央前回、双侧背外侧额上回、双侧眶部额上回、双侧额中回、右侧眶部额中回、双侧岛盖部额下回、左侧补充运动区、左侧嗅皮质、双侧内侧额上回、双侧眶内额上回、双侧回直肌、双侧脑岛、双侧前扣带和旁扣带脑回、右侧内侧和旁扣带脑回、双侧海马、双侧杏仁核、左侧枕中回、左侧枕下回、左侧尾状核、双侧豆状壳核、左侧豆状苍白球、右侧颞上回、双侧颞极:颞上回、双侧颞中回、双侧颞极:颞中回、双侧颞下
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