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)

Aged traumatic brain injury (TBI) patients suffer higher rates of mortality and disability than younger patients. Cognitive problems common to TBI patients are associated with damage to the hippocampus, a central locus of learning and memory. To investigate the molecular mechanisms of age-related vulnerability to brain injury in a mouse model of TBI, we studied the effects of TBI on hippocampal gene expression in young and aged mice. Young and aged male C57Bl/6 mice were subjected to sham injury or TBI and sacrificed 24 h post-injury. We used laser capture microdissection to obtain pure populations of neurons from the CA1, CA3, and dentate gyrus subfields of the hippocampus. We compared injury-induced gene expression in hippocampal neurons of young and aged mice using quantitative ribonuclease protection assay analysis of linearly amplified mRNA from laser captured neurons. Both increased age and TBI were associated with increased expression of neuroprotective (brain-derived neurotrophic factor), pro-inflammatory (interleukin-1beta), and proapoptotic (caspase-3) genes in mouse hippocampal neurons. Our data support previous reports that suggested the CA3 subregion is highly susceptible to fluid percussion TBI and that age-related changes in gene expression are one potential mechanism of increased vulnerability of the aged brain to TBI.
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PMID:Molecular correlates of age-specific responses to traumatic brain injury in mice. 1697 20

Hippocampal damage contributes to cognitive dysfunction after traumatic brain injury (TBI). We previously showed that Fluoro-Jade, a fluorescent stain that labels injured, degenerating brain neurons, quantifies the extent of hippocampal injury after experimental fluid percussion TBI in rats. Coincidentally, we observed that injured neurons in the rat hippocampus also stained with Newport Green, a fluorescent dye specific for free ionic zinc. Here, we show that, regardless of injury severity or therapeutic intervention, the post-TBI population of injured neurons in rat hippocampal subfields CA1, CA3 and dentate gyrus is indistinguishable, both in numbers and anatomical distribution, from the population of neurons containing high levels of zinc. Treatment with lamotrigine, which inhibits presynaptic release of glutamate and presumably zinc that is co-localized with glutamate, reduced numbers of Fluoro-Jade-positive and Newport Green-positive neurons equally as did treatment with nicardipine, which blocks voltage-gated calcium channels through which zinc enters neurons. To confirm using molecular techniques that Fluoro-Jade and Newport Green-positive neurons are equivalent populations, we isolated total RNA from 25 Fluoro-Jade-positive and 25 Newport Green-positive pyramidal neurons obtained by laser capture microdissection (LCM) from the CA3 subfield, linearly amplified the mRNA and used quantitative ribonuclease protection analysis to demonstrate similar expression of mRNA for selected TBI-induced genes. Our data suggest that therapeutic interventions aimed at reducing neurotoxic zinc levels after TBI may reduce hippocampal neuronal injury.
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PMID:Injured Fluoro-Jade-positive hippocampal neurons contain high levels of zinc after traumatic brain injury. 1710 24

The opioid peptide dynorphin (DYN) is expressed normally at high levels in dentate gyrus granule cells in hippocampus and in neurons in entorhinal and neocortex. In the present study, ribonuclease protection and in situ hybridization analyses were used to examine preproDYN mRNA expression in hippocampus and neocortex following recurrent limbic seizure induced by a unilateral electrolytic lesion of the dentate gyrus hilus. In this paradigm, electrographic seizures within hippocampus recur intermittently from 1.6 to 12 h following the hilus lesion (HL). Solution hybridization-ribonuclease protection analysis of preproDYN mRNA levels in hippocampal dentate gyrus/CA1 samples from rats sacrificed 6 and 12 h following HL revealed an approximate 6-fold increase above control values at both times. PreproDYN mRNA levels returned toward control values by 24 h post-HL, were suppressed up to 10-fold below control values at 48 and 96 h post-HL, and then returned to control levels by 10 days post-HL. In situ hybridization analyses confirmed the biphasic nature of seizure-induced changes in preproDYN expression specifically within dentate gyrus granule cells. Additionally, these latter studies demonstrated that seizures induce expression of preproDYN mRNA in a small population of neurons within stratum pyramidale CAL Transient increases in preproDYN mRNA were also detected in subiculum and entorhinal cortex. However, in neocortex hybridization of preproDYN mRNA remained constant through 96 h post-HL. These findings of biphasic seizure-induced alterations in preproDYN mRNA expression can be contrasted with previously described changes in gene expression following limbic seizure activity and suggest that different cellular mechanisms regulate expression of colocalized hippocampal neuropeptides such as dynorphin, Metenkephalin, and neuropeptide Y.
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PMID:Biphasic response of hippocampal dynorphin expression following recurrent limbic seizure. 1991 48

The RNase Dicer is essential for the maturation of most microRNAs, a molecular system that plays an essential role in fine-tuning gene expression. To gain molecular insight into the role of Dicer and the microRNA system in brain function, we conducted 2 complementary RNA-seq screens in the hippocampus of inducible forebrain-restricted Dicer1 mutants aimed at identifying the microRNAs primarily affected by Dicer loss and their targets, respectively. Functional genomics analyses predicted the main biological processes and phenotypes associated with impaired microRNA maturation, including categories related to microRNA biology, signal transduction, seizures, and synaptic transmission and plasticity. Consistent with these predictions, we found that, soon after recombination, Dicer-deficient mice exhibited an exaggerated seizure response, enhanced induction of immediate early genes in response to different stimuli, stronger and more stable fear memory, hyperphagia, and increased excitability of CA1 pyramidal neurons. In the long term, we also observed slow and progressive excitotoxic neurodegeneration. Overall, our results indicate that interfering with microRNA biogenesis causes an increase in neuronal responsiveness and disrupts homeostatic mechanisms that protect the neuron against overactivation, which may explain both the initial and late phenotypes associated with the loss of Dicer in excitatory neurons.
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PMID:Blocking miRNA Biogenesis in Adult Forebrain Neurons Enhances Seizure Susceptibility, Fear Memory, and Food Intake by Increasing Neuronal Responsiveness. 2559 82


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