RESUMEN

BACKGROUND: Fragile X syndrome (FXS), caused by CGG-repeat expansion in FMR1 promoter, is one of the most common causes of mental retardation. Individuals with full mutation and premutation alleles have a high risk of psychophysiological disorder and of having affected offspring. Frequencies of FMR1 alleles in general newborns have been reported in Caucasians but have not been investigated in the large-scale population in  the mainland of China. METHODS: The sizes of FMR1 CGG-repeats were analyzed in 51,661 newborns (28,114 males and 23,547 females) and also in a cohort of 33 children diagnosed with developmental delay using GC-rich polymerase chain reaction (PCR) and triple repeat primed PCR. RESULTS: The frequency of CGG repeats > 100 was 1/9371 in males and 1/5887 in females, and the frequency of CGG repeats > 54 was 1/1561 in males and 1/1624 in females. FMR1 full mutation and premutation were identified in 27.27% of children who had Ages and Stages Questionnaire scores less than two standard deviations from the cutoff value. CONCLUSIONS: Our study revealed the prevalence of FXS in China and improved the sample databases of FXS, suggesting that the prevalence of FXS in Chinese is higher than estimated previously and that FXS screening can be advised to high-risk families.

Asunto(s)

RESUMEN

BACKGROUND: As the third most abundant element, aluminum is widespread in the environment. Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive function. AIM: To study the effects of aluminum on epigenetic modification in neural stem cells and neurons. METHODS: Neural stem cells were isolated from the forebrain of adult mice. Neurons were isolated from the hippocampi tissues of embryonic day 16-18 mice. AlCl3 at 100 and 200 µmol/L was applied to stem cells and neurons. RESULTS: Aluminum altered the differentiation of adult neural stem cells and caused apoptosis of newborn neurons while having no significant effects on the proliferation of neural stem cells. Aluminum application also significantly inhibited the dendritic development of hippocampal neurons. Mechanistically, aluminum exposure significantly affected the levels of DNA 5-hydroxy-methylcytosine, 5-methylcytosine, and N6-methyladenine in stem cells and neurons. CONCLUSION: Our findings indicate that aluminum may regulate neuronal development by modulating DNA modifications.

RESUMEN

BACKGROUND: Autism spectrum disorder (ASD), a pervasive developmental neurological disorder, is characterized by impairments in social interaction and communication, and stereotyped, repetitive patterns of interests or behaviors. The mechanism of ASDs is complex, and genetic components and epigenetic modifications play important roles. In this review, we summarized the recent progresses of ASDs focusing on the genetic and epigenetic mechanisms. We also briefly discussed current animal models of ASD and the application of high-throughput sequencing technologies in studying ASD. DATA SOURCES: Original research articles and literature reviews published in PubMed-indexed journals. RESULTS: Individuals with ASDs exhibit a set of phenotypes including neurological alteration. Genetic components including gene mutation, copy-number variations, and epigenetic modifications play important and diverse roles in ASDs. The establishment of animal models and development of new-generation sequencing technologies have contributed to reveal the complicated mechanisms underlying autistic phenotypes. CONCLUSIONS: Dramatic progress has been made for understanding the roles of genetic and epigenetic components in ASD. Future basic and translational studies should be carried out towards those candidate therapeutic targets.

Asunto(s)

RESUMEN

BACKGROUND: Function of epigenetic modifications is one of the most competitive fields in life science. Over the past several decades, it has been revealed that epigenetic modifications play essential roles in development and diseases including developmental diseases. In the present review, we summarize the recent progress about the function of epigenetic regulation, especially DNA and RNA modifications in developmental diseases. DATA SOURCES: Original research articles and literature reviews published in PubMed-indexed journals. RESULTS: DNA modifications including methylation and demethylation can regulate gene expression, and are involved in development and multiple diseases including Rett syndrome, Autism spectrum disorders, congenital heart disease and cancer, etc. RNA methylation and demethylation play important roles in RNA processing, reprogramming, circadian, and neuronal activity, and then modulate development. CONCLUSIONS: DNA and RNA modifications play important roles in development and diseases through regulating gene expression. Epigenetic components could serve as novel targets for the treatment of developmental diseases.

Asunto(s)

RESUMEN

The anomalous solubility maximum of CO2 in polymer thin films in the vicinity of the critical temperature and pressure has not yet been clearly understood when the quartz crystal microbalance (QCM) technique has been used to determine the micromass change. In this study, the adsorption of CO2 on the surface of bare polished and unpolished crystals at different pressures and temperatures was investigated using the QCM technique to illustrate why a plot of the true frequency shift as a function of temperature and pressure can intuitively exhibit the adsorption behavior of CO2 on bare crystals. The sorption of CO2 into a PMMA film at different temperatures, pressures, and PMMA film thicknesses was also investigated. An accurate solubility for CO2 in the PMMA film could be obtained by an improved data correction method from the linear relation between the true frequency shift and the polymer film mass, and the anomalous solubility maximum could be corrected by this method. The mechanism of nonabsorbed CO2 transitorily staying in the interspace between the PMMA film and the crystal surface can be explained by the morphology change of the PMMA film. The assumption of "passerby CO2" was satisfactorily confirmed to explain the anomalous sorption behavior of CO2 into PMMA films in the vicinity of the CO2 critical temperature and pressure, and this assumption could be valid for other CO2-polymer thin film systems.

RESUMEN

AIM: To investigate the abilities of recombinant adeno-associated virus type 2 (rAAV2) transfecting neurospheres. METHODS: The rAAV2 conjugated with FITC (rAAV2-FITC) was added into the culture medium of neurospheres and 30 minutes later the neurospheres were detected with a fluorescence microscopy to determine if the AAV can combine with neurospheres. The rAAV2 containing GFP reporter gene (rAAV2-GFP) was incubated with the neurospheres for a month and then detected the ability of transfecting neurospheres. The neurospheres transfected with rAAV2-containing GFP were transplanted to the brain of rats. A month later the rats were sacrificed and the brains were removed to detect if there are expressions of the reporter gene. The neurospheres were transfected with rAAV2 containing hypoxia responds elements (HRE) and vascular endothelium growth factor(VEGF) gene and reporter gene GFP (rAAV2-HRE-VEGF-GFP) and then cultured in low oxygen density environments. Seventy-two hours later the neurospheres were detected through a fluorescence microscopy. RESULTS: The neurospheres incubated with rAAV2-FITC present bright green fluorescence. GFP, the reporter gene, can be seen clearly 1 month after being transfected with rAAV2-GFP. The same green fluorescence protein can be observed ex vivo as well. The fluorescence can be seen in neurospheres transfected by rAAV2-HREVEGF-GFP only in low oxygen density. CONCLUSION: The rAAV2 can transfect neurospheres specifically and efficiently. Reporter gene can be expressed in the neurospheres in vivo and ex vivo. Expression of reporter gene can be adjusted by HRE.

Asunto(s)

RESUMEN

AIM: To determine survival and differentiation of cultured neural stem cells (NSCs) into viable and functional neurons upon transplantation into mice brain of MPTP-induced Parkinson disease (PD). METHODS: Mouse model of PD was established with two subcutaneous (sc) injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 40 mg/kg) twice, 16 h apart. NSCs isolated from rat embryo midbrain were cultured in clonal density. After labeled with 5-bromo-2'-deoxyuridine (BrdU), the NSCs were transplanted into the uni- or bi-lateral striatum of PD mouse. Tyrosine hydroxylase (TH) immunofluorescence was used to evaluate the toxicity of MPTP on the neural cells in the substantia nigra. Immunohistology and laser confocal microscope were used to detect the survival and differentiation of transplanted NSCs. RESULTS: The cultured NSCs generated neurospheres and differentiated into neuron and astrocyte. It indicated that the cultured NSCs were multipotent and self-renewal in vitro. TH-positive neural cells were significantly reduced in the substantia nigra. Immunohistology showed that the uni- or bi-lateral transplanted NSCs survived in the brain of PD model mouse. Laser confocal microscope indicated that some transplanted NSCs could properly differentiate into targeted TH-positive neural cells in vivo. CONCLUSION: The transplanted multipotent NSCs could survive and differentiate into functional dopamine neurons.

Asunto(s)