Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zinc transporters (ZnTs) and plasticity-related genes (PRGs) both play the key roles in the formation of hippocampal mossy fiber sprouting, which is associated with cognitive deficits following developmental seizures. Here, for the first time, we report the timing of expression pattern of ZnT-1, ZnT-3 and PRG-1 in hippocampus and cerebral cortex following developmental seizures. A seizure was induced by inhalant flurothyl daily in neonatal Sprague-Dawley rats from postnatal day 6 (P6). Rats were assigned into the recurrent-seizure group (RS, seizures induced in 6 consecutive days) and the control group. At 1.5 h, 3 h, 6 h, 12 h, 24 h, 48 h, 7 d and 14 d after the last seizures, the mRNA level was detected using RT-PCR method; PRG-1 protein level was examined by Western blotting analysis. At an early period of 12 h and 48 h after the last seizures, both ZnT-1 and ZnT-3 showed significantly down-regulated mRNA level in the cerebral cortex of RS group than those at the corresponding time point in control group. In the long-term time point of 14 d after the last seizure, ZnT-3 mRNA and PRG-1 protein level in hippocampus were up-regulated while the mRNA level of ZnT-1 down-regulated; in addition, there were up-regulated level of both the mRNA and protein level of PRG-1 and down-regulated mRNA level of ZnT-3 in the cerebral cortex of RS group when compared to the control. Taken together, these dates are consistent with an important role for ZnT-1, ZnT-3 and PRG-1 in the pathophysiology of the long-term adverse effects of recurrent neonatal seizure-induced hippocampal mossy fiber sprouting and cognitive deficit.
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PMID:Dynamic pattern of gene expression of ZnT-1, ZnT-3 and PRG-1 in rat brain following flurothyl-induced recurrent neonatal seizures. 2016 68

Cathepsins are families of proteases that have been reported to play the key roles in neuroexcitotoxicity. The present study was sought to determine the effect of CBI, a cathepsin B inhibitor, in the prevention of neurobehavioral deficits after inhalant flurothyl-induced recurrent neonatal seizures in rats. We examined the expression pattern of autophagy-related genes at acute phase after the last seizures using western blot method, and evaluated behavioral deficits during postnatal day 28 (P28) to P35. The results showed improved neurological scores and learning ability in CBI-treated rats compared with the nontreated control. Flurothyl-induced increases in the ratio of LC3-II/LC3-I, Beclin-1 and Cathepsin-B were blocked by pre-treatment with CBI at 1.5, 3, 6 and 24 h after the last seizures in hippocampus and cerebral cortex by western blot analysis. Meanwhile, CBI also reversed flurothyl-induced down-regulation of Bcl-2 protein levels. Furthermore, in the long-term time point of 35 days (P35), PRG-1 mRNA and protein level in hippocampus and cerebral cortex of recurrent seizure group were up-regulated when compared to the control rats; meanwhile, the up-regulated expression of PRG-1 were robustly inhibited by CBI. These date demonstrated, for the first time, that lysosomal enzymes participate in neonatal seizure-induced brain damage and that modulation of cathepsin B may offer a new strategy for the development of therapeutic interventions for treatment of developmental seizure-induced brain damage.
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PMID:Long-term effects of recurrent neonatal seizures on neurobehavioral function and related gene expression and its intervention by inhibitor of cathepsin B. 2184 68

E-64d (a calpain and autophagy inhibitor) has previously been shown safe for the treatment of Alzheimer's disease in humans. In the present study, the potential protective mechanism of E-64d on hippocampal aberrant mossy fiber sprouting was examined in a developmental rat model of penicillin-induced recurrent epilepticus. A seizure was induced by penicillin every other day in Sprague-Dawley rats from postnatal day 21 (P21). The rats were randomly assigned into the control group (CONT1), the control plus E-64d (CONT2), the seizure group (EXP1) and the seizure plus E-64d (EXP2). On P51, mossy fiber sprouting and related gene expression in hippocampus were assessed by Timm staining and real-time RT-PCR methods, respectively. To validate the RT-PCR results, western blot analysis was performed on selected genes. E-64d obviously suppressed the aberrant mossy fiber sprouting in the supragranular region of dentate gyrus and CA3 subfield of hippocampus. Among the total twelve genes, six genes were strongly up- (MT-3, ACAT1, clusterin and ApoE) or down- (ZnT-1 and PRG-3) regulated by developmental seizures (EXP1) compared with that in the CONT1. Up-regulation of ApoE and Clusterin was blocked by pretreatment with E-64d both in mRNA and protein levels. Further, E-64d-pretreated seizure rats (EXP2) showed a significant downregulation of mRNA expression of PRG-1, PRG-3 and PRG-5, cathepsin B and ApoE, as well as up-regulated nSMase and ANX7 in hippocampus when compared with EXP1 rats. The results of the present study suggest that E-64d, an elective inhibitor of calpain and autophagy, is potentially useful in the treatment of developmental seizure-induced brain damage both by regulating abnormal zinc signal transduction and through the modulation of altered lipid metabolism via ApoE/clusterin pathway in hippocampus.
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PMID:Expression profiles of hippocampal regenerative sprouting-related genes and their regulation by E-64d in a developmental rat model of penicillin-induced recurrent epilepticus. 2326 20