Expression Alteration of PLP2 in the Process of Cardiac Remodeling / 医学研究杂志

Objective To investigate the expression of PLP2 protein in the process of cardiac remodeling.Methods Mice were subjected to left anterior descending coronary artery ligation to induce cardiac remodeling model.Mice were subjected to isoproterenol (ISO) subcutaneous injection for 2 weeks to establish acute cardiac injury model.Mice were subjected to aortic banding (AB) surgery to establish a myocardial hypertrophy model.Cardiac myocytes hypertrophy model was induced by phenylephrine (PE) stimulation.Transforming growth factor (TGF) beta was used to stimulate cardiac fibroblasts.The PLP2 transcription level was detected by RT-PCR.Results PLP2 expression was significantly increased in 2 weeks after myocardial infarction (P ＜ 0.05),as well as in acute cardiac injury induced by ISO injection (P ＜ 0.05).After 1 week of AB surgery,the PLP2 expression began to increase (P ＜ 0.05),peaked at 2 weeks post AB (P ＜ 0.05),preserved to 8 weeks after AB (P ＜ 0.05).The expression of PLP2 in PE stimulated cardiomyocytes was increased as well as TGFβ stimulated fibroblast.Conclusion The expression of PLP2 were dynamically changed significantly in different cardiac remodeling model,suggesting that it may be involved in the occurrence and development of cardiac remodeling.

Research progress of genotype and phenotype in proteolipid protein 1-related disorders / 中华实用儿科临床杂志

Proteolipid protein 1 (PLP1)-related disorders are a series rare X-linked recessive disorders caused by mutations of PLP1 gene.There is a spectrum of PLP1-related disorders from very severe connatal PelizaeusMerzbacher disease(PMD,MIM# 312080),through classical PMD to mild spastic paraplegia type 2 (SPG2,MIM# 312920),with some correlation between the type of mutation and the phenotype.The genotype of PLP1-related disorders was constantly discovered and updated,meanwhile there was obvious heterogeneous within clinical phenotypes.Moreover,there were so many diseases similar to PLP1-related disorders.Therefore,there was a huge challenge when clinician met with PLP1-related disorders.The aim of this report is to summarize correlation between the genotype and the phenotype of PLP1-related disorders,and give a help for clinician to diagnose this group complicated disorders.

Effect of GPR56 on axonal development and myelination / 中华急诊医学杂志

Objective To determine the likelihood of G-protein coupled receptor 56 (GPR56 ) induces axonal development and myelination in the corpus callosum of mouse brain.Methods A total of 64 Gpr56 +/-and Gpr56 -/-mice were selected and randomly divided into two groups:Gpr56 +/-group (n=32)and Gpr56 -/-group (n=32).According to number of days after birth,each group was further divided into 4 subgroups including P7d,P14d,P21d and P28d subgroups.Levels of neurofilament-200 (NF -200)and proteolipid protein (PLP ) of myelin basic protein in corpus callosum were measured with immunohistochemistry staining and Western blot in P7d、P14d、P21d、P28d Gpr56 +/- and Gpr56 -/-mice.Gpr56 +/-and Gpr56 -/-neurons were cultured using P1 d Gpr56 +/-and Gpr56 -/-mouse brain.The lengths of Gpr56 +/- and Gpr56 -/-neuronal axon were measured and compared with Image J software. Axonal myelination in the corpus callosum of mouse brain in each group was observed under electronic microscopy and the axonal diameters between subgroups were compared.Results The levels of NF-200 and PLP in the corpus callosum in P7d、P14d、P21d、P28d Gpr56 -/-mice decreased significantly compared with Gpr56 +/- mice.The length of Gpr56 -/-neuronal axon was shortened compared with Gpr56 +/-neuronal axon.The number of myelinated axons was obviously reduced in the corpus callosum in P28d Gpr56 -/-mice.The diameter of axon in the corpus callosum of P28d Gpr56 +/-mouse is longer than that of P28d Gpr56 -/-mouse. Conclusions GPR56 may be involved in axonal development and myelination in the corpus callosum of mouse brain.

Gene mutations and prenatal diagnosis in six pedigrees with Pelizaeus-Merzbacher disease / 中华围产医学杂志

Objective To investigate proteolipid protein 1 (PLP1) mutations in six pedigrees with Pelizaeus-Merzbacher disease (PMD),and to provide prenatal consulting and prenatal diagnosis.Methods Subjects were six probands with PMD admitted in Department of Pediatrics,Peking University First Hospital from July 2006 to November 2011 and their family members.Genomic DNA sarnples were extracted from peripheral bloods of probands and their family members.Multiplex ligation-dependent probe amplification (MLPA) technique was used to detect PLP1 duplication mutation.Direct DNA sequencing was used to detect point mutation.Genetic diagnosis were based on PLP1 mutation genotype from probands.Prenatal diagnosis of nine fetuses were performed from seven PLP1 mutation female carriers by fetuses' DNA extracted from amniocytes or villus cells.Results PLP1 duplications were found in probands 1-4 (P1-4) whose mothers and the aunt of proband 1 (P1) were PLP1 duplications carriers.The two cases of point mutation,c.96C＞G(p.F32L) and c.623G＞T (p.G208V),were found in proband 5 (P5) and proband 6 (P6).Hcterozygous changes of the same mutations were found in P5' and P6' mothers with normal phenotypes.Seven female PLP1 mutation carriers were pregnant again.Prenatal diagnosis of PLP1 for nine fetuses presented one PLP1 duplication,one point mutation,one PLP1 duplication carrier,and six wildtypes.A segmental crossing over of X chromosome was detected in one male fetus of PLP1 wildtype.Conclusions PLP1 mutation analysis could help to diagnose PMD pedigree and to identify female PLP1 mutation carrier in the family.The following prenatal diagnosis and proper genetic counseling are very important to prevent PMD child from being delivered.

Magnetic resonance imaging and spectroscopic analysis in 5 cases of Pelizaeus-Merzbacher disease: metabolic abnormalities as diagnostic tools / 소아과

Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked recessive disorder characterized by dysmyelination in the central nervous system. PMD results from deletion, mutation, or duplication of the proteolipid protein gene (PLP1) located at Xq22, leading to the failure of axon myelination by oligodendrocytes in the central nervous system. PMD may be suspected when there are clinical manifestations such as nystagmus, developmental delays, and spasticity, and genetic analysis can confirm the diagnosis. Further diagnostic manifestations of the disease include a lack of myelination on brain magnetic resonance (MR) imaging and aberrant N-acetyl aspartate (NAA) and choline concentrations that reflect axonal and myelination abnormalities on phroton MR spectroscopy. We report 5 cases of PMD (in 1 girl and 4 boys). PLP1 duplication was detected in 2 patients. Brain MR analyses and MR spectroscopy were performed for all the patients. The brain MR images showed white matter abnormalities typical of PMD, and the MR spectroscopic images showed diverse patterns of NAA, creatinine, and choline concentrations. We propose that MR spectroscopic analysis of metabolic alterations can aid the PMD diagnosis and can contribute to a better understanding of the pathogenesis of the disease.

Ethanol down regulates the expression of myelin proteolipid protein in the rat hippocampus / 대한해부학회지

It is well known that chronic ethanol treatment affects the synthesis of RNA and protein in the brain and the maintenance and function of nervous system. The changes in myelination-related genes are most prominent in human alcoholics. Previously, our cDNA microarray study showed altered Proteolipid protein (PLP), a major protein of central myelin. The present study aimed to gain more understanding of the expression of PLP after chronic ethanol treatment. Male Sprague-Dawley rats were daily treated with ethanol (15% in saline, 3 g/kg, i.p.) or saline for 14 days. Messenger RNAs from hippocampus of each group were subjected to cDNA expression array hybridization to determine the differential gene expressions. Among many ethanol responsive genes, PLP was negatively regulated by ethanol treatment, which is one of the most abundant proteins in the CNS and has an important role in the stabilization of myelin sheath. Using northern blot and immunohistochemical analysis, we showed the change in expression level of PLP mRNA and protein after ethanol treatment. PLP mRNA and protein were decreased in hippocampus of rat with chronic ethanol exposure, suggesting that ethanol may affect the stabilization of myelin sheath through the modulation of PLP expression and induce the pathophysiology of alcoholic brain.

Gene expression profile in mice model of experimental autoimmune encephalomyelitis using cDNA microarrays / 中华神经科杂志

Objective To construct the genes expression profile database of experimental autoimmune encephalomyelitis (EAE) mice model and to screen the high candidate genes with microarray analysis. Methods Polymerase chain reaction (PCR) products on behalf of 4 096 genes from mixed mice tissue library were assembled on the modified Oako glass slide. The general RNA from 6 EAE mice model and 6 normal mice head was transcripted into cDNA by RT-PCR and labelled with cy-3 and cy-5.6 groups each consist one EAE mice and a control. These two probes were mixed and hybridized with the above mentioned gene chips. Scan array 4000 was used for scanning the hybridizing signals and GenePixPro 3.0 for date analysis. Results Of the total 4 096 genes monitored, 43 genes in group one showed changes in expression level of the ratio outside 0.5 and 2, 30 genes differed in group two, 176 genes changed in group three, 76 in group four, 294 in group five and 129 in group six. Conclusions The results showed the consistent different genes expression throughout the EAE mice model. The genes related to immune, cell structure, cell cycle, ion channel, signal transduction, protein synthesis and metabolism are involved in EAE pathogenesis. The results provide deeper insights into the mechanism of EAE and multiple sclerosis.