Dynamic pattern of gene expression of ZnT-1, ZnT-3 and PRG-1 in rat brain following flurothyl-induced recurrent neonatal seizures

Hóng, Ní; Jiang, Yuwu; Xiao, Zhuo-jun; Tao, Luyang; Jin, Meifang; Wu, Xiru

doi:10.1016/j.toxlet.2010.02.008

Cited by 22 publications

(18 citation statements)

References 49 publications

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“…Deletion of prg-1 in mice leads to epileptic seizures and augmentation of EPSCs, which suggests PRGs as important players in the modulatory control of hippocampal excitability [31]. In a recently published paper from our laboratory, we reported for the first time that flurothyl inhalation-induced neonatal seizures caused significant elevation of PRG-1 expression in cerebral cortex 14 days after the last seizure [32]. This is just in accordance with our present results.…”

Section: Discussionsupporting

confidence: 92%

Long-term Effects of Recurrent Neonatal Seizures on Neurobehavioral Function and Related Gene Expression and Its Intervention by Inhibitor of Cathepsin B

et al. 2011

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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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Section: Discussionsupporting

confidence: 92%

Long-term Effects of Recurrent Neonatal Seizures on Neurobehavioral Function and Related Gene Expression and Its Intervention by Inhibitor of Cathepsin B

et al. 2011

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“…Increased autophagy has been reported in experimental models of traumatic brain injury, stroke, and excitotoxicity and in patients with Alzheimer's disease and critical illness [8]. We have previously demonstrated disturbed expression pattern of ZnT-1 and ZnT-3 following recurrent neonatal seizures [9][10][11]. Besides, we also found that over-stimulation of KA receptors can activate autophagy [12].…”

Section: Introductionmentioning

confidence: 68%

Acute Phase Expression Pattern of ZnTs, LC3, and Beclin-1 in Rat Hippocampus and Its Regulation by 3-Methyladenine Following Recurrent Neonatal Seizures

Hóng

Feng

Gong

et al. 2010

Biol Trace Elem Res

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It has been reported that autophagy and zinc transporters (ZnTs) both play the key roles in excitotoxicity, which is associated with cognitive deficits following developmental seizures. However, the influence of autophagy on acute phase ZnTs expression has never been studied. The present study sought to investigate the contribution of an autophagy inhibitor (3-methyladenine, 3-MA) on the regulation of ZnTs, microtubule-associated protein 1A/1B light chain 3 (LC3), and beclin-1 expression in rat hippocampus following recurrent neonatal seizures. We examined the expression of ZnT1~ZnT3, LC3, and beclin-1 at 1.5, 3, 6, and 24 h after the last seizures using real-time RT-PCR and Western blot methods, respectively. The results showed that there were upregulated expressions of ZnT-1, ZnT-2, LC3, and beclin-1 of RS group. Pretreatment with 3-MA remarkably attenuated seizure-induced ZnT-1, ZnT-2, LC3, and beclin-1 increase. Additionally, linear correlations could be observed between LC3-Beclin1, LC3-ZnT-2, Beclin1-ZnT2, Beclin1-ZnT3, and among ZnT1~ZnT3 in control group, while the linear correlations could be observed between LC3-Beclin1, Beclin1-ZnT2, and Beclin1-ZnT3 in RS group. These results demonstrate, for the first time, that there exists an interaction of Zn(2+) with autophagic signals that are immediately activated in hippocampus after recurrent neonatal seizures, which might play a key role in neonatal seizure-induced excitotoxicity.

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“…Increased autophagy has been reported in experimental models of traumatic brain injury, stroke, and excitotoxicity and in patients with Alzheimer's disease and critical illness [10]. We have previously demonstrated disturbed expression pattern of ZnT-1 and ZnT-3 following recurrent neonatal seizures [11][12][13]. Besides, we also found that over-stimulation of KA receptors can activate autophagy [14].…”

Section: Introductionmentioning

confidence: 68%

“…However, the expression and the significance of ZnT-4 in neurological diseases are seldom investigated. We have previously reported for the first time that the alteration in developmental seizure-induced impairment of cognition and sprouting of mossy fibers is paralleled by a decreased level of GluR2, which render neurons highly sensitive to Ca 2+ -mediated AMPA neurotoxicity, and ZnT1, which is responsible for the 3,5,7,9,11,13, and 15 are the corresponding time points in control group. Densitometry analysis of the mRNA concentration using gene/β-actin was expressed as the mean with SD in each column indicated in the last panel (n=6 per group).…”

Section: Discussionmentioning

confidence: 99%

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Dynamic Pattern of Gene Expression of ZnT-4, Caspase-3, LC3, and PRG-3 in Rat Cerebral Cortex Following Flurothyl-Induced Recurrent Neonatal Seizures

Hóng

Feng

Xiao

et al. 2011

Biol Trace Elem Res

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Zinc transporters, plasticity-related genes, and autophagic/apoptotic pathway both are associated with developmental seizure-induced brain excitotoxicity. Here, for the first time, we report the timing of expression pattern of zinc transporter 4 (ZnT-4), plasticity-related gene 3 (PRG-3), specific marker of autophagic vacuoles (LC3), and apoptotic marker caspase-3 in cerebral cortex following neonatal 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 six consecutive days) and the control group. At 1.5 h, 3 h, 6 h, 12 h, 24 h, 48 h, 7 days, and 14 days after the last seizure, the mRNA level of the four genes in cerebral cortex was detected using RT-PCR method. At an early period 6 h or 12 h after the last seizures, both ZnT-4 and LC3 showed significantly up-regulated mRNA level while PRG-3 showed significantly down-regulated mRNA level at 12 h in cerebral cortex of RS group than those at the corresponding time point in control group. In the long-term time point of 7 days after the last seizure, the mRNA level of caspase-3 down-regulated; meanwhile, there was up-regulated mRNA level of LC-3 in RS group when compared to the control rats. This is the first report investigating the gene expression pattern of ZnT-4, PRG-3, LC-3, and caspase-3 in the developing brain. The results suggest that the disturbed expression pattern of the four genes might play a role in the pathophysiology of recurrent neonatal seizure-induced acute and long-term brain damage.

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Dynamic pattern of gene expression of ZnT-1, ZnT-3 and PRG-1 in rat brain following flurothyl-induced recurrent neonatal seizures

Cited by 22 publications

References 49 publications

Long-term Effects of Recurrent Neonatal Seizures on Neurobehavioral Function and Related Gene Expression and Its Intervention by Inhibitor of Cathepsin B

Long-term Effects of Recurrent Neonatal Seizures on Neurobehavioral Function and Related Gene Expression and Its Intervention by Inhibitor of Cathepsin B

Acute Phase Expression Pattern of ZnTs, LC3, and Beclin-1 in Rat Hippocampus and Its Regulation by 3-Methyladenine Following Recurrent Neonatal Seizures

Dynamic Pattern of Gene Expression of ZnT-4, Caspase-3, LC3, and PRG-3 in Rat Cerebral Cortex Following Flurothyl-Induced Recurrent Neonatal Seizures

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