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

Global cerebral ischemia following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) causes injury to hippocampal CA1 pyramidal neurons and impairs cognition. Small conductance Ca(2+)-activated potassium channels type 2 (SK2), expressed in CA1 pyramidal neurons, have been implicated as potential protective targets. Here we showed that, in mice, hippocampal long-term potentiation (LTP) was impaired as early as 3 h after recovery from CA/CPR and LTP remained impaired for at least 30 days. Treatment with the SK2 channel agonist 1-Ethyl-2-benzimidazolinone (1-EBIO) at 30 min after CA provided sustained protection from plasticity deficits, with LTP being maintained at control levels at 30 days after recovery from CA/CPR. Minimal changes in glutamate release probability were observed at delayed times after CA/CPR, implicating post-synaptic mechanisms. Real-time quantitative reverse transcriptase-polymerase chain reaction indicated that CA/CPR did not cause a loss of N-methyl-D-aspartate (NMDA) receptor mRNA at 7 or 30 days after CA/CPR. Similarly, no change in synaptic NMDA receptor protein levels was observed at 7 or 30 days after CA/CPR. Further, patch-clamp experiments demonstrated no change in functional synaptic NMDA receptors at 7 or 30 days after CA/CPR. Electrophysiology recordings showed that synaptic SK channel activity was reduced for the duration of experiments performed (up to 30 days) and that, surprisingly, treatment with 1-EBIO did not prevent the CA/CPR-induced loss of synaptic SK channel function. We concluded that CA/CPR caused alterations in post-synaptic signaling that were prevented by treatment with the SK2 agonist 1-EBIO, indicating that activators of SK2 channels may be useful therapeutic agents to prevent ischemic injury and cognitive impairments.
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PMID:Increasing small conductance Ca2+-activated potassium channel activity reverses ischemia-induced impairment of long-term potentiation. 2508 Feb 3

Learning and memory impairment is one of the most challenging complications of cirrhosis and present treatments are unsatisfactory. The exact mechanism of cirrhosis cognitive dysfunction is unknown. Pregnenolone sulfate (PREGS) is an excitatory neurosteroid that acts as a N-methyl-D-aspartate (NMDA) receptor agonist and GABAA receptor antagonist. In this study we evaluated the effect of intra CA1 infusion of PREGS on cirrhotic rats' memory function using the Y-maze test. Hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression was also evaluated. Three weeks after bile duct ligation (BDL) surgery, rats were under stereotaxic surgery for insertion of two guide cannulas in the CA1 region of the hippocampus. After 1-week of recovery, PREGS was administered through CA1 cannulas in cirrhotic rats, while control or sham groups received vehicle. For evaluation of NMDA receptor role in memory-enhancing effects of PREGS, DL-2-Amino-5-phosphonopentanoic acid (AP5) which is a potent and competitive antagonist of NMDA receptor, co-administered with PREGS and for assessment of hippocampal BDNF mRNA expression, quantitative Real-time reverse transcriptase-PCR (RT-PCR) was used. Results showed that 28 days after BDL, cirrhotic animals' memory significantly decreased in comparison with control and sham groups, while PREGS infusion could restore memory impairment (P<0.05). PREGS effects on memory of cirrhotic rats were antagonized by DAP5. RT-PCR findings have shown that hippocampal relative BDNF mRNA expression was up-regulated in PREGS-treated groups in comparison with the BDL group (P<0.001). Our findings suggest that PREGS has a memory-enhancing effect in cirrhosis memory deficit in acute therapy and this effect may be through NMDA (glutamate) receptor involvement and BDNF mRNA expression.
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PMID:The effects of intra-dorsal hippocampus infusion of pregnenolone sulfate on memory function and hippocampal BDNF mRNA expression of biliary cirrhosis-induced memory impairment in rats. 2627 34

The review focuses on transcriptomic changes following treatment with serotonin reuptake inhibitor (SSRI) antidepressants. We aimed to overview results of the most established methods for the investigation of the gene expression alterations including northern blotting, in situ hybridization, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), microarray and RNAseq in various brain regions and after chronic treatment protocols. In spite of some measurable changes in serotonin system mRNA expression, serotonin transporter levels remained mostly unaltered following various treatment protocols. In contrast, tryptophan hydroxylase 2 appeared to be downregulated in serotonergic nuclei, and upregulated in the midbrain regions. Alterations in serotonin receptors lack clear conclusions and changes probably reflect animal strain/substance related- and brain region dependent effects. Brain derived neurotrophic factor was upregulated following many, but not all chronic treatment regimens. GABA and glutamate genes also showed heterogeneous changes, with a surprising NMDA receptor downregulation in areas including the striatum and amygdala, known to be involved in depressive states and stress reactions. The review of the above studies suggests alterations in multiple processes, reflecting the heterogeneity of the action depending on brain area and type of SSRI, and raises the possibility of a novel grouping of antidepressant medications based on their chronic molecular profile rather than on their initial actions.
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PMID:Transcriptomic changes following chronic administration of selective serotonin reuptake inhibitors: a review of animal studies. 3096 7


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