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Temporal lobe epilepsy (TLE) is a devastating disease in which aberrant synaptic plasticity plays a major role. We identify matrix metalloproteinase (MMP) 9 as a novel synaptic enzyme and a key pathogenic factor in two animal models of TLE: kainate-evoked epilepsy and pentylenetetrazole (PTZ) kindling-induced epilepsy. Notably, we show that the sensitivity(More)
Matrix metalloproteinase-9 has recently emerged as an important molecule in control of extracellular proteolysis in the synaptic plasticity. However, no synaptic targets for its enzymatic activity had been identified before. In this report, we show that beta-dystroglycan comprises such a neuronal activity-driven target for matrix metalloproteinase-9. This(More)
The occurrence, nature and prevention of ammonia-induced cell death were assayed in cultured primary cortical neurons from newborn rats. Treatment with 1-10 mM ammonium chloride for 24 or 48 h, dose-dependently decreased neuronal survival (MTT assay) and GSH/GSSG ratio in the cultures, whereas total GSH content was significantly reduced only with 10mM(More)
The acronym ICER (inducible cAMP early repressor) refers to a group of four proteins produced from the CREM/ICER gene due to use of an internal promoter (P2) placed in an intron of the CREM (cAMP responsive element modulator) gene. The ICER proteins contain DNA binding/leucine zipper domains that make them endogenous inhibitors of transcription driven by(More)
Membrane depolarization controls long lasting adaptive neuronal changes in brain physiology and pathology. Such responses are believed to be gene expression-dependent. Notably, however, only a couple of gene repressors active in nondepolarized neurons have been described. In this study, we show that in the unstimulated rat hippocampus in vivo, as well as in(More)
Cyclic AMP response element binding protein (CREB) is a constitutive transcription factor that activates transcription following stimulus-dependent phosphorylation at Ser133, implicated in synaptic plasticity and neuronal survival pathways. The prevailing view that CREB is exclusively nuclear has been questioned by several studies, and, for example,(More)
Active CREB (cAMP responsive element-binding protein) transcription factor is crucial for neuronal survival. Several members of the CREM/ICER (cAMP responsive element modulator/inducible cAMP early repressor) protein family may act as endogenous CREB antagonists. However, their involvement in a process of programmed cell death remains unexplored. Here we(More)
Programmed cell death involving gene regulation and de novo protein synthesis is a major component of both normal development and a number of disease conditions. Hence, knowledge of its mechanisms, especially transcription factors, that regulate expression of the genes involved in neurodegenerative disorders is of great importance. cAMP-responsive(More)
To advance our understanding of the central nervous system, there is a need for refined approaches to control gene expression in neuronal culture as well as in the brain in vivo. In this study, we have applied a doxycycline-responsive Tet system to obtain a tightly controlled gene expression in neurons. In the absence of doxycycline, the Tet promoter-driven(More)
Cisplatin, a widely used chemotherapeutic is approved for the management of various solid tumors. Administration of cisplatin is associated with induction of significant toxicities that include neurotoxicity and nephrotoxicity, the latter leading to severe and debilitating anemia. Since erythropoietin, a hematopoietic growth factor that corrects(More)
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