Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Traumatic brain injury (TBI) is a major cause of disability in the pediatric population and can result in abnormal development. Experimental studies conducted in animals have revealed impaired plasticity following developmental TBI, even in the absence of significant anatomical damage. The N-methyl-D-aspartate receptor (NMDAR) is clearly involved in both normal development and in the pathophysiology of TBI. Following lateral fluid percussion injury in postnatal day (PND) 19 rats, we tested the hypothesis that TBI sustained at an early age would result in impaired NMDAR expression. Using immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR), protein and RNA levels of NMDAR subunits were measured in the cerebral cortex and hippocampus on post-injury days (PID) 1, 2, 4, and 7 (though the PID7 analysis was only for protein) and compared with age-matched shams. Significant effects of hemisphere (analysis of variance [ANOVA], p<0.01), and interactions between hemisphere and injury (ANOVA, p<0.05) and hemisphere and PID (ANOVA, p<0.05) were found for synaptic protein levels of the NR2A subunit in hippocampus. Specifically, within the ipsilateral hippocampus, NR2A was reduced by 9.9%, 47.9%, 40.8%, and 6.3% on PID1, PID2, PID4, and PID7, respectively. Within the cortex, there was a significant effect of injury (ANOVA, p<0.05) without any hemispheric differences. These bilateral cortical reductions measured 30.5%, 3.2%, 5.7%, and 13.4% at the same timepoints after injury. Injury had no significant main effect on NR1 or NR2B protein levels. RT-PCR analysis showed no significant changes in NR1, NR2A, or NR2B gene expression; however, as a positive control, hsp70 was induced more than twofold in ipsilateral cortex and hippocampus on PID1. It is known that NR2A expression levels increase during normal development, and in response to environmental stimuli. Our data suggest that injury-induced reduction in the expression of NR2A is one likely mechanism for the impaired experience-dependent neuroplasticity seen following traumatic injury to the immature brain.
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PMID:N-methyl-D-aspartate receptor subunit changes after traumatic injury to the developing brain. 1677 79

Peripheral inflammation causes production of central cytokines that alter transmission at the N-methyl-D-aspartate receptor (NR). During development, NRs are important for synaptic plasticity and network connectivity. We therefore asked if neonatal inflammation would alter expression of NRs in the brain and behavioural performance in adulthood. We gave lipopolysaccharide (LPS) (100 microg/kg, i.p.) or saline to male rats on postnatal day (P)5, P14, P30 or P77. Subsequently we assessed mRNA levels of the NR1, NR2A, B, C and D subunits in the hippocampus and cortex either acutely (2 h) or in adulthood using real-time reverse transcriptase-polymerase chain reaction. We explored learning and memory behaviours in adult rats using the Morris water maze and contextual fear conditioning paradigms. Hippocampal NR1 mRNA was acutely increased in the P5- and P77-treated rats but was reduced in adults treated with LPS at P5, P30 and P77. P14 LPS-treated rats showed few acute changes but showed pronounced increases in NR2A, B, C and D subunit mRNA later in adulthood. The cortex displayed relatively few acute changes in expression in the neonatal-treated rats; however, it showed robust changes in NR2B, C and D mRNA in all groups given LPS in adulthood. Behavioural deficits were observed specifically in the P5 and P30 LPS-treated groups in the water maze probe trial and fear conditioning tests, consistent with hippocampal NR1 mRNA down-regulation. Thus, a single bout of inflammation during development can programme specific and persistent differences in NR mRNA subunit expression in the hippocampus, which could be associated with behavioural and cognitive deficits in adulthood.
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PMID:Neonatal inflammation produces selective behavioural deficits and alters N-methyl-D-aspartate receptor subunit mRNA in the adult rat brain. 1827 17

Subunit composition of N-methyl-D-aspartate-type glutamate receptors (NMDARs) dictates their function, yet the ontogenic profiles of human NMDAR subunits from gestation to adulthood have not been determined. We examined NMDAR mRNA and protein development in human dorsolateral prefrontal cortex (DLPFC), an area in which NMDARs are critical for higher cognitive processing and NMDAR hypofunction is hypothesized in schizophrenia. Using quantitative reverse transcriptase-polymerase chain reaction and western blotting, we found NR1 expression begins low prenatally, peaks in adolescence, yet remains high throughout life, suggesting lifelong importance of NMDAR function. In contrast, NR3A levels are low during gestation, surge soon after birth, and decline progressively through adolescence and into adulthood. Because NR3A subunits uniquely attenuate NMDAR-mediated currents, limit calcium influx, and suppress dendritic spine formation, high levels during early childhood may be important for regulating neuroprotection and activity-dependent sculpting of synapses. We also examined whether subunit changes underlie reduced NMDAR activity in schizophrenia. Our results reveal normal NR1 and NR3A protein levels in DLPFC from schizophrenic patients, indicating that NMDAR hypofunction is unlikely to be maintained by gross changes in NR3A-containing NMDARs or overall NMDAR numbers. These data provide insights into NMDAR functions in the developing CNS and will contribute to designing pharmacotherapies for neurological disorders.
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PMID:Developmental regulation of the NMDA receptor subunits, NR3A and NR1, in human prefrontal cortex. 1829 32

Embryonal carcinoma (EC) cells have proven to be of particular value in studies of both oncogenesis and mammalian development, as well as in evaluating the relationship between these two phenomena. Infection of the EC cell line, NR1-0, with a defective retrovirus containing a neomycin resistance cassette (Neo(r)), produced a mutant cell line: NR1-6. Genetic analysis of this variant cell line indicates that there is only a single insertion site. Interestingly, however, the NR1-6 cell line is unique in its morphology, tumorigenicity, and differentiative potential (1). We have sequenced over 18 kb from the regions flanking the retroviral insertion which we then analyzed using the computer programs GCG and BLAST. Although homology was found to 4 B1 repeat elements (approximately 150 bp long) and a novel CA/GT dinucleotide repeat, no homology was found to any known genes (2). Furthermore, attempts to identify potential exons or transcripts using various molecular techniques and the above mentioned computer programs were all negative. Most recently we employed the GRAIL (Gene Recognition and Analysis Internet Link) computer program which was specifically designed to identify potential exons (3). Analysis with this program identified 5 exon candidates: two characterized as excellent (>90% probability) and three as marginal (>60% probability). Using reverse transcriptase (RT)-PCR we have demonstrated that the two 'excellent' and one of the 'marginal' exon candidates identified by GRAIL are expressed as mRNA in the mutant cells. Sequencing of these PCR products indicates that the mRNA is identical to the genomic DNA sequence. Thus, we have found that GRAIL provides an efficient, reliable means of identifying real exons within long regions of novel genomic DNA.
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PMID:Identification of exons in a novel embryonal carcinoma locus using the GRAIL program. 2159 76

We studied the effects of water deprivation (WD) on the phosphorylation of tyrosine kinase B (TrkB) and NMDA receptor subunits in the supraoptic nucleus (SON) of the rat. Laser capture microdissection and quantitative reverse transcriptase polymerase chain reaction was used to demonstrate brain-derived neurotrophic factor (BDNF) and TrkB gene expression in vasopressin SON neurones. Immunohistochemistry confirmed BDNF staining in vasopressin neurones, whereas staining for phosphorylated TrkB was increased following WD. Western blot analysis of brain punches containing the SON revealed that tyrosine phosphorylation of TrkB (pTrkBY(515)), serine phosphorylation of NR1 (pNR1S(866) or pNR1) and tyrosine phosphorylation of NR2B subunits (pNR2BY(1472) or pNR2B) were significantly increased in WD animals compared to controls. Access to water for 2 h reduced pTrkBY(515) content to control levels without affecting pNR1 or pNR2B. Four hours of rehydration was needed to reduce pNR1 and pNR2B to control levels. To test whether increased phosphorylation of TrkB in the present study is mediated by BDNF, a group of animals were instrumented with right SON cannula coupled to mini-osmotic pumps filled with vehicle or TrkB-Fc fusion protein, which prevents BDNF binding to TrkB. In the left SON contralateral to the cannula, TrkB phosphorylation was significantly enhanced following WD. Separate analysis of the right SON, which received TrkB-Fc, showed that the TrkB receptor phosphorylation following WD was significantly attenuated. Although increased pNR1S(866) following WD was not affected by local infusion of TrkB-Fc, pNR2BY(1472) was significantly reduced. Co-immunoprecipitation revealed an increased physical interaction between Fyn kinase and NR2B and TrkB in the SON following WD. Thus, activation of TrkB in the SON following WD may affect cellular excitability through the phosphorylation of NR2B subunits.
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PMID:Brain-derived neurotrophic factor-tyrosine kinase B pathway mediates NMDA receptor NR2B subunit phosphorylation in the supraoptic nuclei following progressive dehydration. 2184 49


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