Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain-derived neurotrophic factor (BDNF) regulates neuronal survival, differentiation and plasticity. It has been shown to promote epileptogenesis and transgenic mice with decreased and increased BDNF signaling show opposite alterations in epileptogenesis. However, the mechanisms of BDNF action are largely unknown. We studied the gene expression changes 12 days after kainic acid-induced status epilepticus in transgenic mice overexpressing either the functional BDNF receptor trkB or a dominant-negative truncated trkB. Epileptogenesis produced marked changes in expression of 27 of 1090 genes. Cluster analysis revealed BDNF signalling-mediated regulation of functional gene classes involved in cellular transport, DNA repair and cell death, including kinesin motor kinesin family member 3A involved in cellular transport. Furthermore, the expression of cytoskeletal and extracellular matrix components, such as tissue inhibitor of metalloproteinase 2 was altered, emphasizing the importance of intracellular transport and interplay between neurons and glia during epileptogenesis. Finally, mice overexpressing the dominant-negative trkB, which were previously shown to have reduced epileptogenesis, showed a decrease in mRNAs of several growth-associated genes, including growth-associated protein 43. Our data suggest that BDNF signaling may partly mediate the development of epilepsy and propose that regrowth or repair processes initiated by status epilepticus and promoted by BDNF signaling may not be as advantageous as previously thought.
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PMID:Brain-derived neurotrophic factor signaling modifies hippocampal gene expression during epileptogenesis in transgenic mice. 1521 81

MicroRNAs (miRNAs) are reported to involve in pathogenesis of temporal lobe epilepsy (TLE). miR-142-5p is found increased in TLE, but its role remains unknown. In the study, we established a mouse model of status epilepticus (SE) with pilocarpine and a cell model of TLE. Quantitative real-time PCR revealed an up-regulation of miR-142-5p and down-regulation of mitochondrial Rho 1 (Miro1) in the mouse mode of SE. Administration of miR-142-5p antagomirs via intracerebroventricular injection attenuated pilocarpine-induced SE and hippocampal damage, and alleviated mitochondrial dysfunction along with increased mitochondrial membrane potential and intracellular ATP and Ca (2+) levels. The expression of mitochondrial trafficking kinesin protein (Trak) 1 and Trak2 was up-regulated by inhibiting miR-142-5p. Antagomirs targeting miR-142-5p suppressed pilocarpine-induced oxidative stress as evidenced by decreased ROS generation and MPO activity, and increased SOD activity. Silencing miR-142-5p reduced neuronal death in pilocarpine-treated hippocampus and magnesium-free (MGF)-treated neurons. Inhibition of miR-142-5p decreased cytoplasmic Cytochrome C and increased mitochondrial Cytochrome C, reduced cleaved-caspase3 and Bax levels, and elevated Bcl2 in vivo and in vitro. Further, dual-luciferase assay verified Miro1 as a target of miR-142-5p, suggesting that miR-142-5p might function via targeting Mrio1. Depletion of Miro1 inhibited the protective effect of silencing miR-142-5p on hippocampal neurons in vitro. Taken together, down-regulation of miR-142-5p via targeting Miro1 inhibits neuronal death and mitochondrial dysfunction, and thus attenuates pilocarpine-induced SE, suggesting the potential involvement of miR-142-5p in the pathogenesis of TLE.
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PMID:Antagomirs targeting miR-142-5p attenuate pilocarpine-induced status epilepticus in mice. 3243 93