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Age- and area-dependent distinct effects of ethanol on Bax and Bcl-2 expression in prenatal rat brain

Authors
Lee, Hae YoungNaha, NibeditaKim, Jong HunJo, Mi JaMin, Kwan SikSeong, Hwan HooShin, Dong HoonKim, Myeong Ok
Issue Date
9월-2008
Publisher
KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY
Keywords
Bax; Bcl-2; ethanol; prenatal rat brain; programmed cell death
Citation
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, v.18, no.9, pp.1590 - 1598
Indexed
SCIE
SCOPUS
KCI
Journal Title
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
Volume
18
Number
9
Start Page
1590
End Page
1598
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/122789
ISSN
1017-7825
Abstract
Cell proliferation and differentiation are critical processes in a developing fetal rat brain, during which programmed cell death (PCD) also plays an important role. One of the decisive factors for PCD is Bcl-2 family proteins, where Bax induces cell death, whereas Bcl-2 acts as an inhibitor of PCD. As maternal drinking is known to cause fetal alcohol syndrome (FAS) or malformation of the fetal brain during pregnancy, the objective of the present study was to investigate whether maternal ethanol exposure alters the PCD-related Bax and Bcl-2 protein expression during fetal brain development. Pregnant female rats were orally treated with 10% ethanol and the subsequent expressions of the Bax and Bcl-2 proteins examined in the fetal brain, including the forebrain, midbrain, and hindbrain, from gestational day (GD) 15.5 to GD 19.5, using Western blots, in situ hybridization, and immunohistochemistry. With regard to the ratio of Bcl-2 to Bax proteins (Bcl-2/Bax), the Bax protein was dominant in the forebrain and midbrain of the control GD 15.5 fetuses, except for the hindbrain, when compared with the respective ethanol-treated groups. Moreover, Bcl-2 became dominant in the midbrain of the control GD 17.5 fetuses when compared with the ethanol-treated group, representing an alternation of the natural PCD process by ethanol. Furthermore, a differential expression of the Bcl-2 and Bax proteins was found in the differentiating and migrating zones of the cortex, hippocampus, thalamus, and cerebellum. Thus, when taken together, the present results suggest that ethanol affects PCD in the cell differentiation and migration zones of the prenatal rat brain by modulating Bax and Bcl-2 expression in an age- and area-dependent manner. Therefore, this is the first evidence that ethanol may alter FAS-associated embryonic brain development through the alteration of Bax and Bcl-2 expression.
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