Long‑term expression of zinc transporters in hippocampus following penicillin‑induced developmental seizures and its regulation by E‑64d

Ni,Hong; Zhang,Le‑Ling; Ren,Shou‑Yun; Sun,Bao‑Liang

doi:10.3892/etm.2016.3276

Long‑term expression of zinc transporters in hippocampus following penicillin‑induced developmental seizures and its regulation by E‑64d

Authors:
- Hong Ni
- Le‑Ling Zhang
- Shou‑Yun Ren
- Bao‑Liang Sun
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Affiliations: Neurology Laboratory, Institute of Pediatrics, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China, Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Department of Neurology, Affiliated Hospital of Taishan Medical College, Taian, Shandong 271000, P.R. China
Published online on: April 20, 2016 https://doi.org/10.3892/etm.2016.3276
Pages: 208-214
Copyright: © Ni et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Autophagy has been shown to be involved in the pathophysiology of developmental seizure‑induced brain damage. The present study aimed to examine whether E‑64d, an autophagy inhibitor, was able to facilitate developmental seizure‑induced hippocampal mossy fiber sprouting, in particular sprouting‑associated zinc transporter signals. Recurrent seizures were induced by penicillin every other day in Sprague‑Dawley rats from postnatal day 21 (P21). Rats were randomly assigned into the control group (CONT), recurrent seizure group (RS) and the seizure plus E‑64d group (E64D). The expression levels of beclin‑1 and B‑cell lymphoma 2 were analyzed at 1.5, 3, 6 and 24 h after the last seizures using western blot analysis. At P51, mossy fiber sprouting and the mRNA expression levels of zinc transporter 2 (ZnT‑2), ZnT‑4, ZnT‑5, ZnT‑6, ZnT‑7, divalent cation transporter 1, Zrt‑Irt‑like protein 6 (ZIP‑6), ZIP‑7, cathepsin D and cathepsin L in the rat hippocampus were assessed using Timm staining and reverse transcription‑quantitative polymerase chain reaction analysis, respectively. Reduced hippocampal mossy fiber sprouting were detected in the E‑64d‑treated rats compared with the non‑treated control. In parallel with these observations, there was a marked reduction in the mRNA expression levels of ZnT‑4 at P51 in the E‑64d‑treated rat hippocampus compared with the non‑treated seizure group. Linear correlation analysis showed significant inter‑relationship among ZIP‑7, ZnT‑4, ZnT‑5, ZnT‑7, cathepsin D and cathepsin L. These results indicate that the ZnT‑4/ZIP‑7/cathepsin signaling pathway serves a crucial function in the neuroprotective effects of E‑64d. Thus, E‑64d may offer a novel strategy for the development of therapeutic interventions for developmental seizure‑induced brain damage.

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