Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetically engineered cells carrying genes for neurotrophic factors have potential application for treatment of neurodegenerative diseases and injuries to the nervous system. Brain-derived neurotrophic factor (BDNF) promotes the survival of specific neurons, including retinal ganglion cells (RGC). To determine whether genetically engineered astrocytes might be used for delivering bioactive BDNF, we infected primary type 1 rat astrocytes with a retrovirus harboring a human prepro-BDNF cDNA and assayed the medium conditioned by these astrocytes for effects on survival of rat RGCs in vitro. High levels of BDNF mRNA were expressed by infected astrocytes, but not by control astrocytes as determined by RNase protection assay using a BDNF specific probe. To test for secretion of bioactive BDNF from the transgenic astrocytes, embryonic day 17 rat retinas were dissociated and grown in medium conditioned (CM) for 24 h by astrocytes infected with a replication deficient retrovirus carrying BDNF, NGF, or alkaline phosphatase (AP) cDNA. After 3 days, the number of Thy-1 immunoreactive RGCs was counted. BDNF astrocyte CM significantly enhanced RGC survival by 15-fold compared to the AP control. NGF astrocyte CM had no significant effect. The rate of BDNF secretion was estimated at 83-166 pg/10(5) cells/h. This study demonstrates that astrocytes can be genetically engineered to synthesize and secrete bioactive BDNF. These techniques may be applicable to rescuing neurons from degenerative processes and also for enhancing their survival following transplantation.
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PMID:Retinal ganglion cell survival is promoted by genetically modified astrocytes designed to secrete brain-derived neurotrophic factor (BDNF). 806 2

Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of high-frequency synaptic transmission and long-term potentiation in the hippocampus, processes that are also thought to be involved in the learning of spatial tasks such as the Morris water maze. In order to determine whether BDNF is required for normal spatial learning, mice carrying a deletion in one copy of the BDNF gene were subjected to the Morris water maze task. Young adult BDNF mutant mice were significantly impaired compared with wild-type mice, requiring twice the number of days to reach full performance. Aged wild-type mice performed significantly worse than young wild-type mice and the effect was even more pronounced in the BDNF mutant mice, which did not learn at all. Although there was no difference in mean swimming speed between BDNF mutant and wild-type mice, we cannot exclude the possibility that developmental or peripheral deficits also contribute to the learning deficits in these mice. In situ hybridization and RNase protection analysis revealed that BDNF mRNA expression was indeed decreased in BDNF mutant mice. Furthermore, a pronounced effect of age on BDNF mRNA expression was seen, displayed as both a reduced level of mRNA expression and a reduced or entirely absent layer-specific expression pattern in the cerebral cortex of aged animals. Thus, our data suggest that BDNF expression may be linked to learning.
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PMID:Learning deficit in BDNF mutant mice. 951 63

Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, regulate synaptic functions in the hippocampus of the adult rodent. In previous studies, in situ hybridization methods have been used to evaluate regional differences in BDNF and trkB mRNA expression levels in hippocampal subregions. However, these studies have failed to reach consensus regarding the regional differences in the mRNA expression levels. In the present study, we quantitated mRNA expression levels using two different methods, ribonuclease protection assays and a quantitative reverse-transcription polymerase chain reaction technique, in four hippocampal subregions: the entorhinal cortex, dentate gyrus (DG), CA3 and CA1. These two methods yielded the same results. We found that BDNF and trkB mRNA expression levels did not covary in the four subregions. BDNF and full length trkB (trkB FL) mRNA in the entorhinal cortex and the DG show contrasting expression patterns. The expression level of BDNF mRNA was highest in the DG among the hippocampal subregions and low in the entorhinal cortex and the CA1, whereas the trkB FL mRNA expression level was highest in the entorhinal cortex, low in the DG and lowest in the CA3. These results suggest regional differences in BDNF/TrkB signaling for maintenance and modifiability of neuronal connections in the hippocampal formation.
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PMID:Highest trkB mRNA expression in the entorhinal cortex among hippocampal subregions in the adult rat: contrasting pattern with BDNF mRNA expression. 981 29

The present studies were undertaken to characterize the regional and temporal patterns of neurotrophin messenger RNA and protein levels for beta-nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the developing CNS. We have examined the levels of these neurotrophin messenger RNAs with ribonuclease protection assays and corresponding protein levels with enzyme-linked immunosorbent assays in the developing Long-Evans rat hippocampus, neocortex and cerebellum on postnatal days 1, 7, 14, 21, and 92. In addition, immunohistochemistry was used to localize the neurotrophins in these developing brain regions. Results indicated that in neocortex and hippocampus, messenger RNA for both nerve growth factor and brain-derived neurotrophic factor increased in an age-dependent manner, reaching a plateau by postnatal day 14. In the neocortex, nerve growth factor and brain-derived neurotrophic factor protein levels both peaked at postnatal day 14. In hippocampus, nerve growth factor protein peaked at postnatal day 7 while brain-derived neurotrophic factor peaked at postnatal day 14. In cerebellum, nerve growth factor messenger RNA levels were flat, while nerve growth factor protein peaked at postnatal day 7. Brain-derived neurotrophic factor messenger RNA increased in an age-dependent manner while the pattern for its protein levels was mixed. Neurotrophin-3 messeger RNA levels increased in an age-dependent manner in hippocampus, peaked at postnatal day14 in cerebellum, and no changes occurred in neocortex. Neurotrophin-3 protein was at its peak at postnatal day 1 and thereafter decreased at other postnatal days in all three brain regions. Results of neurotrophin immunohistochemistry often paralleled and complemented enzyme-linked immunosorbent assay data, demonstrating specific cell groups containing neurotrophin proteins in these regions. Within each region, patterns with regard to messenger RNA and respective protein levels for each neurotrophin were unique. No consistent relationship between patterns of neurotrophin messenger RNAs and their cognate proteins was observed between regions. The different regional patterns for neurotrophin messengerRNA and protein levels in each brain region indicate that messenger RNA studies of neurotrophin messenger RNA must be augmented by protein determination to fully characterize spatial and temporal neurotrophin distribution.
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PMID:Differential patterns of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNA and protein levels in developing regions of rat brain. 1127 92

Studies were performed to determine the effects of acute and chronic voluntary periods of exercise on the expression of hippocampal genes. RNAs from rodents exposed to a running wheel for 3, 7 and 28 days were examined using a microarray with 1176 cDNAs expressed primarily in the brain. The expression of selected genes was quantified by Taqman RT-PCR or RNase protection assay. The largest up-regulation was observed in genes involved with synaptic trafficking (synapsin I, synaptotagmin and syntaxin); signal transduction pathways (Ca2+/calmodulin-dependent protein kinase II, CaM-KII; mitogen-activated/extracellular signal-regulated protein kinase, MAP-K/ERK I and II; protein kinase C, PKC-delta) or transcription regulators (cyclic AMP response element binding protein, CREB). Genes associated with the glutamatergic system were up-regulated (N-methyl-d-aspartate receptor, NMDAR-2A and NMDAR-2B and excitatory amino acid carrier 1, EAAC1), while genes related to the gamma-aminobutyric acid (GABA) system were down-regulated (GABAA receptor, glutamate decarboxylase GAD65). Brain-derived neurotrophic factor (BDNF) was the only trophic factor whose gene was consistently up-regulated at all timepoints. These results, together with the fact that most of the genes up-regulated have a recognized interaction with BDNF, suggest a central role for BDNF on the effects of exercise on brain plasticity. The temporal profile of gene expression seems to delineate a mechanism by which specific molecular pathways are activated after exercise performance. For example, the CaM-K signal system seems to be active during acute and chronic periods of exercise, while the MAP-K/ERK system seems more important during long-term exercise.
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PMID:Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray. 1238 40

Brain-derived neurotrophic factor (BDNF) is strongly expressed in the hippocampus, where it has been associated with memory processes. In the central nervous system, some learning processes, as well as brain insults, including stress, induce modifications in BDNF mRNA expression. Because stress and memory appear to share some neuronal pathways, we studied BDNF mRNA and BDNF peptide variations in response to short times of immobilization stress. Using an RNase protection assay, we demonstrated that short-time stress application induced a significant increase (at 60 min) in BDNF mRNA levels in the whole rat hippocampus. Changes in BDNF mRNA content appear to reflect increased expression of BDNF transcripts containing exons I, II, and III, that were also significantly modified at this time. The time course of stress-induced changes in BDNF transcript levels revealed that mRNA containing exon III was the first increased, significantly elevated by 15 min, attaining maximal levels at 60 min, as BDNF transcripts containing exons I and II. However, at longer times of stress (180 min), BDNF mRNA levels were decreased as well as mRNA containing exon IV. In situ hybridization analysis of discrete hippocampal layers demonstrated that BDNF mRNA expression increased as early as 15 min in most hippocampal regions, with no modification in the number of labeled cells. The same signal pattern, although less pronounced, was determined at 60 min, but at this time a significant increase in BDNF-positive cells was visualized in the CA3 layer. The peptide, measured by immunoassay, was significantly augmented after 180 min of stress exposure whereas at 300 min, levels were similar to those measured in control animals. These data suggest that rapid changes in BDNF expression may be part of a compensatory response to preserve hippocampal homeostasis or a form of neuronal plasticity to cope with new stimuli.
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PMID:Rapid induction of BDNF expression in the hippocampus during immobilization stress challenge in adult rats. 1292 53