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)

An enriched environment can enhance brain recovery in animals with early-life status epilepticus (SE). The purpose of this study was to determine the effects of early-life SE on spatial memory and hippocampal extracellular signal-regulated kinase (ERK) level, and the possible therapeutic effects of the enriched environment. Rats were assigned randomly to four groups: (1) control rats (nonenriched control); (2) control rats housed in an enriched environment from Postnatal Day (P) 25 to P40 (enriched control); (3) rats in which SE was induced with lithium-pilocarpine (Li-PC) at P21 (nonenriched SE); and (4) rats in which SE was induced with Li-PC at P21 and then housed in an enriched environment from P25 to P40 (enriched SE). As adults, the rats underwent spatial learning and memory tests in the Morris water maze between P50 and P55. At P55, subsets of animals were evaluated for expression of hippocampal ERK1/2 phosphorylation immediately following completion of the Morris water maze. At ~P100, another set of animals was tested for seizure threshold. When studied as adults, only the nonenriched SE group had a spatial memory deficit. The nonenriched SE group also exhibited lower levels of phosphorylated ERK2 as compared with the nonenriched control, enriched control, and enriched SE groups. Both the nonenriched SE and enriched SE groups had reduced seizure thresholds as compared with the nonenriched control and enriched control groups. Results from this study demonstrate that an enriched environment improves spatial memory in rats subjected to early-life SE, possibly through upregulation of phosphorylated ERK2 in the hippocampus. However, an enriched environment has no effect on seizure threshold.
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PMID:An enriched environment improves cognitive performance after early-life status epilepticus accompanied by an increase in phosphorylation of extracellular signal-regulated kinase 2. 1782 56

The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P<0.01). Performance in SE rats was improved with donepezil treatment (P<0.01), but declined with carbamazepine (P<0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P<0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P<0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented this impairment, whereas donepezil was found to ameliorate the dysfunction associated with epilepsy. In conclusion, ERK2 and NCAM1 have significant roles in impairment of spatial memory in SE rats. Carbamazepine may increase this impairment, while donepezil may decrease this impairment.
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PMID:Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction. 2758 25

Recently, we have reported that heat shock protein B1 (HSPB1) and purinergic receptor P2X7 (P2RX7) are involved in astroglial autophagy (clasmatodendrosis), following status epilepticus (SE). However, the underlying mechanisms of astroglial autophagy have not been completely established. In the present study, we found that the lacking of P2rx7 led to prolonged astroglial HSPB1 induction due to impaired mitogen-activated protein kinase 1/2 (MAPK1/2)-mediated specificity protein 1 (SP1) phosphorylation, following kainic acid-induced SE. Subsequently, the upregulated HSPB1 itself evoked ER stress and exerted protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1, AMPK1)/unc-51 such as autophagy activating kinase 1 (ULK1)- and AKT serine/threonine kinase 1 (AKT1)/glycogen synthase kinase 3 beta (GSK3B)/SH3-domain GRB2-like B1 (SH3GLB1)-mediated autophagic pathways, independent of mechanistic target of rapamycin (MTOR) activity in astrocytes. These findings provide a novel purinergic suppression mechanism to link chaperone expression to autophagy in astrocytes. Therefore, we suggest that P2RX7 may play an important role in the regulation of autophagy by the fine-tuning of HSPB1 expression.
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PMID:P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy. 2974 77