Lamotrigine prevents MK801-induced alterations in early growth response factor-1 mRNA levels and immunoreactivity in the rat brain
- Authors
- Park, Sang-Ha; Seo, Young Ho; Moon, Bo-Hyun; Choi, Song-hyen; Kang, Seungwoo; Lee, Kuem-Ju; Choi, Sang-Hyun; Lee, Min-Soo; Chun, Boe-Gwun; Shin, Kyung-Ho
- Issue Date
- 28-7월-2008
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- early growth response factor-1; MK801; lamotrigine; retrosplenial cortex
- Citation
- EUROPEAN JOURNAL OF PHARMACOLOGY, v.589, no.1-3, pp.58 - 65
- Indexed
- SCIE
SCOPUS
- Journal Title
- EUROPEAN JOURNAL OF PHARMACOLOGY
- Volume
- 589
- Number
- 1-3
- Start Page
- 58
- End Page
- 65
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/123009
- DOI
- 10.1016/j.ejphar.2008.04.059
- ISSN
- 0014-2999
- Abstract
- MK801 (dizocilpine) induces selective neurotoxic effects in the retrosplenial cortex, ranging from neuronal vacuolization to irreversible neurodegeneration depending on the dose administered. Although lannotrigine prevents MK801-induced neuronal vacuolization in the retrosplenial cortex 4 h after injection, it is not clear whether lamotrigine attenuates the subsequent neu rod egene ration that occurs 3-4 days later. Because early growth response factor-1 (egr-1) plays a key role in neurodegeneration and its expression is induced in the retrosplenial cortex following MK801 treatment, it is possible that lamotrigine may attenuate MIK801-induced neurodegeneration via inhibition of egr-1 expression in the retrosplenial cortex. To address this issue, we treated rats with lamotrigine (10 or 20 mg/kg) followed by MK801 (2 mg/kg) and measured changes in the levels of egr-1 mRNA and immunoreactivity, in the retrosplenial cortex and other brain regions 3 h later. We also evaluated the effects of these treatments on neurodegeneration 4 days following treatment using Fluoro-jade B staining. MK801 treatment increased egr-1 mRNA and immunoreactivity in the restrosplenial, cingulate, entorhinal and piriform cortices, but decreased levels in hippocampal subfields. These MK801 -induced changes in egr-1 expression were significantly inhibited by lamotrigine pretreatment. In addition, MK801-induced neurodegeneration in the retrosplenial cortex was partially blocked by lamotrigine pretreatment in a dose dependent manner. These results demonstrate that lamotrigine pretreatment prevents the MK801 -induced upregulation of egr-1 expression in a region-selective manner, and suggest that this effect may contribute, in part, to the attenuation of MK801 -induced neurodegeneration in the retrosplenial cortex. (C) 2008 Elsevier B.V. All rights reserved.
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