ZnT-1, ZnT-3, CaMK II, PRG-1 expressions in hippocampus following neonatal seizure-induced cognitive deficit in rats

Hóng, Ní; Jiang, Yuwu; Tao, Luyang; Jin, Meifang; Wu, Xiru

doi:10.1016/j.toxlet.2008.11.003

Cited by 26 publications

(32 citation statements)

References 16 publications

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“…We have previously characterized the neurobehavioral and histopathological effects of flurothyl seizure-induced brain damage, with an emphasis on a phenotypic anchor of excitatory/inhibitory gene expression to neurobehavioral injury, especially cognitive deficit [11,14,15]. However, the impact of neonatal seizures on autophagic gene expression has not been characterized and the question remains as to whether or not autophagic mechanism participates in developmental seizure-induced brain damage.…”

Section: Discussionmentioning

confidence: 99%

“…The procedure of seizure induction has been described in detail previously [10,11]. Briefly, seizures were induced in the neonatal rats with volatile flurothyl (bis-2, 2, 2-triflurothyl ether, Aldrich-Sigma Chemical, WI, USA), a potent and rapidly acting central nervous system stimulant that produces seizures within minutes of exposure.…”

Section: Animal Preparationmentioning

confidence: 99%

“…The procedure has been described in detail [11]. The rats were placed in a closed area with the floor divided into 64 equal squares (100 cm 2 ).…”

Section: Open Field Testmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Animal Preparationmentioning

confidence: 99%

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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 [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%

“…We have recently revealed that flurothyl-induced recurrent neonatal seizures caused longterm influence in ZnT-1, ZnT-3, and PRG-1 expression in cerebral cortex of adult rats that is paralleled by cognitive dysfunction and mossy fiber sprouting [11]. Until now, however, there is no study investigating the dynamic pattern of mRNA expression of ZnT-4, LC-3, caspase-3, and PRG-3 following developmental seizures.…”

Section: Discussionmentioning

confidence: 99%

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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Effects of Forced Running Exercise on Cognitive Function and Its Relation to Zinc Homeostasis-Related Gene Expression in Rat Hippocampus

Hóng

Feng

2010

Biol Trace Elem Res

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Voluntary exercise has been implicated to be beneficial for overall health and cognitive function in both clinical and experimental studies, but little is presently known about forced physical exercise on cognition and underlying molecular mechanism. We have used real-time RT-PCR to analyze gene expression in hippocampus, in the presence and absence of physical exercise, during spatial learning of rats in the Morris water maze. Our results show distinct zinc homeostasis-related gene expression profiles associated with learning and memory. Rats with physical exercise (EXP) showed a significant up-regulation of mRNA expression of zinc transporter-2 (ZnT-2), ZnT-4, ZnT-5, ZnT-6, and ZnT-7, metallothionein-1 (MT-1)-MT-3, divalent cation transporter-1, and Zrt-Irt-like proteins-7 in hippocampus when compared with control rats. In addition, spatial learning ability was improved in EXP rats compared with that in control group. This study provides the first comparative view of zinc homeostasis-related gene expression in hippocampus following forced physical exercise. These results suggested that forced physical exercise may provide a simple means to maintain brain function and promote learning capacity. Results of this study also suggest that exercise mobilizes zinc homeostasis-related gene expression profiles that would be predicted to benefit brain plasticity processes.

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ZnT-1, ZnT-3, CaMK II, PRG-1 expressions in hippocampus following neonatal seizure-induced cognitive deficit in rats

Cited by 26 publications

References 16 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

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

Effects of Forced Running Exercise on Cognitive Function and Its Relation to Zinc Homeostasis-Related Gene Expression in Rat Hippocampus

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