Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-irradiation to neuronal progenitor cells causes brain dysfunctions, such as a mental retardation, in adulthood. However, little has been known about the degree of radiosensitivity of neurons in the developmental stages at which they are most vulnerable. In this study we compared the effect of irradiation on mature neurons with that on immature neurons. Primary dissociated neuronal cultures were prepared from fetal rat hippocampi of embryonic day 18. X-irradiations were performed on the cultured cells at 7 or 21 days in vitro (DIV), and the cells were fixed at 12 or 24 h after irradiation. Then the cells were stained with 4',6-diamidino-2-phenylindole (DAPI) or terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The apoptotic changes were measured quantitatively by nuclear pyknosis and DNA fragmentation-both characteristic morphological changes of apoptosis. Light microscopy with differential interference contrast showed that 30 Gy of irradiation increased cellular shrinkage in 7-DIV neurons but not in 21-DIV neurons. Quantitative analysis using DAPI imaging showed that 30 Gy of irradiation significantly enhanced pyknotic changes in 7-DIV neurons after 24 h. In contrast, this irradiation did not enhance any pyknotic changes in 21-DIV neurons after 24 h. Further TUNEL staining also showed that the irradiation did not enhance any DNA fragmentation in nuclei of 21-DIV neurons after 24h. Hence, we showed that the radiosensitivity of 21-DIV postmitotic neurons was significantly lower than that of 7-DIV neurons, indicating that the susceptibility of such neurons depends on their developmental stage.
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PMID:Differential effects of x-irradiation on immature and mature hippocampal neurons in vitro. 1648 15

Alcohol affects approximately 1% (40,000) of new born infants each year and is the main preventable cause of mental retardation in the US. Ethanol alters cell signaling and promotes apoptosis and differentiation. Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family of growth factors, has been reported to prevent apoptosis and differentiation. We treated human embryonic stem cells (hESCs) with ethanol (20 mM) to reflect casual drinking, with and without HB-EGF to measure its ability to prevent ethanol-induced apoptosis and differentiation. Apoptosis was measured by DNA fragmentation (terminal dUTP nick-end labeling assays) and activated caspase-3, while differentiation was accessed by SSEA-1 and OCT-3/4; western blotting assessed MAPK signaling. HB-EGF reduced SSEA-1 and elevated OCT-3/4, while reducing the amount of activated caspase-3 and DNA fragmentation. Western blot analysis showed HB-EGF prevents ethanol from altering MAPK phosphorylation. This data suggests that ethanol-induced apoptosis was reduced by HB-EGF, while hESC pluripotency was maintained.
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PMID:Heparin binding epidermal growth factor-like growth factor reduces ethanol-induced apoptosis and differentiation in human embryonic stem cells. 1991 24