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)

At 4 h during pilocarpine-induced status epilepticus (DPISE) in rat, protein kinase C (PKC)beta1, PKCbeta2, and PKCgamma were induced at the border between the stratum oriens and alveus (O/A border) of CA1 in the hippocampus. Induced PKCgamma was colocalized with metabotropic glutamate receptor alpha (mGluR alpha). By intracerebroventricular injection of mGluR1alpha antagonists, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), PKCbeta1, PKCbeta2, and PKCgamma immunoreactive products decreased dramatically; however, intracerebroventricular injection of saline did not change the expression of PKCbeta1, PKCbeta2, and PKCgamma, suggesting that these three PKC isoforms might be involved in mGluR1alpha-related excitoneurotoxicity. One day after pilocarpine-induced status epilepticus (APISE), PKCdelta was induced in microglial cells. At this time point, both PKCgamma and PKCepsilon immunopositive products decreased in the inner molecular layer of upper blade of the stratum granulosum. At 7-31 days APISE, induced PKCbeta1, PKCdelta, PKCeta, and PKCzeta positive astrocytes were demonstrated in all parts of hippocampus, suggesting that they may be involved in gliosis. By this time, both PKCgamma and PKCepsilon immunopositive products in the inner molecular layer had almost disappeared, suggesting that they may be involved in the inhibition of granule cells by controlling neurotransmitter release presynaptically in the dentate gyrus of normal rats.
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PMID:Expression of different isoforms of protein kinase C in the rat hippocampus after pilocarpine-induced status epilepticus with special reference to CA1 area and the dentate gyrus. 1505 86

While it is generally accepted that phospholipase C (PLC) and protein kinase C (PKC) are down-stream proteins involved in metabotropic glutamate receptor 5 (mGluR5)-related signal transduction, we still do not know which subtype of PLC or PKC is specifically regulated after mGluR5 activation. In the present study in mGluR5 wild-type (mGluR5+/+) mice, we showed induced PKCbeta2 or PKCgamma expression at the border between the stratum oriens and alveus (O/A border) at 2h during pilocarpine induced status epilepticus (SE), and in the stratum pyramidale in CA1 area at 1 day after pilocarpine induced SE; at 1 day, induced expression of PLCbeta4 in the stratum pyramidale of CA1 area was observed. Furthermore, double labeling revealed the co-localization of induced PKCbeta2 or PKCgamma with mGluR5 or with induced PLCbeta4 in the stratum pyramidale of CA1 area. These induced expression, however, were not found in mGluR5 mutant (mGluR5-/-) mice. It suggests that induced PLCbeta4-PKCbeta2/PKCgamma at 1 day after pilocarpine induced SE in pyramidal neurons or PKCbeta2 or PKCgamma in interneurons at O/A border at 2h during pilocarpine induced SE may be specifically linked to the activation of mGluR5. When compared to mGluR5+/+ mice, significant shorter latency (from pilocarpine injection to the occurrence of status epilepticus) and maintenance period (from beginning to the end of status epilepticus) for status epilepticus in mGluR5-/- mice were also demonstrated. It is possible that mGluR5 may play a negative role in initiation of status epilepticus by interacting with muscarinic acetylcholine receptor in mGluR5+/+ mice.
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PMID:mGluR5-PLCbeta4-PKCbeta2/PKCgamma pathways in hippocampal CA1 pyramidal neurons in pilocarpine model of status epilepticus in mGluR5+/+ mice. 1877 62

Status epilepticus (SE) is associated with complex reorganization of hippocampal circuits involving a significant loss of specific subtypes of GABAergic interneurons. While adaptive circuit plasticity may increase the chances for recruitment of surviving interneurons, the underlying mechanisms remain largely unknown. We studied the alterations in the inhibitory tone received by the hippocampal CA1 oriens/alveus (O/A) interneurons from the vasoactive intestinal peptide (VIP)- and calretinin (CR)-expressing interneurons using the pilocarpine-induced status epilepticus (SE) model of epilepsy. Our data showed that, while the overall density of the VIP/CR-co-expressing interneurons remained preserved, the number of axonal boutons made by these cells within the CA1 O/A was significantly lower after SE. Furthermore, VIP/CR interneurons exhibited significant alterations in their dendritic morphology and passive membrane properties. Subsequently, while all O/A interneuron types, including oriens-lacunosum moleculare (OLM), bistratified (Bis) and basket cells, exhibited decrease in spontaneous inhibitory drive, Bis and basket cells showed a smaller amplitude of light-evoked IPSCs mediated by the selective activation of VIP-positive interneurons. These data point to the target cell-specific changes in the inhibitory tone provided by the VIP cells to O/A interneurons following SE. Given that basket, Bis and OLM cells coordinate different subcellular domains of pyramidal neurons, significant disinhibition of basket and Bis cells along with a previously reported loss of the OLMs may result in a redistribution of inhibition converging onto pyramidal neurons, with a direct impact onto their recruitment to epileptiform network activity and seizure propagation.
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PMID:Target-specific alterations in the VIP inhibitory drive to hippocampal GABAergic cells after status epilepticus. 2831 8