Temporal Changes in the Expression of BAX and BCL-2, and the Sub-regional Vulnerability to Cellular Apoptosis after a Binge-like Ethanol Exposure in the Developing Rattus norvegicus Hippocampus

Alcohol;FAS;FASD;Ethanol;Binge-drink;Apoptosis;Hippocampus

Smith, Caine Christopher ; Napper, Ruth

University of Otago

关键词: Alcohol;    FAS;    FASD;    Ethanol;    Binge-drink;    Apoptosis;    Hippocampus;   

Others  :  https://ourarchive.otago.ac.nz/bitstream/10523/4415/1/SmithCaineC2013MSc.pdf

美国|英语

来源: Otago University Research Archive

【 摘 要 】

Exposure to ethanol in utero can result in life-long disability. Ethanol is neurotoxic, and exposure of high doses during development results in widespread cell death. A particular brain region of interest that is affected is the hippocampus, which has implications in learning and memory. The present study uses a rat model of binge-like drinking, during the third trimester-equivalent stage of neural development of humans, to investigate cell death in the hippocampus. The optical fractionator method was used to estimate total acute apoptotic cell death in the CA1, CA3, and DG sub-regions of the hippocampus. Rat pups were given ethanol on PN6 and PN8, or on PN8 only, and tissue was collected 12 hours after the last ethanol exposure. Furthermore, relative expression of apoptotic proteins Bcl-2 and Bax was measured in the CA1/DG and CA3 sub-regions 12, 24, and 48 hours after ethanol exposure on PN6.These experiments showed significant cell death in all sub-regions of the hippocampus after a single, exposure on PN8 only, with a lot less cell death following a PN8 exposure, which was preceded by a PN6 exposure. The Bcl-2:Bax ratio significantly increased at the 24 hour time point, and returned back to control levels by 48 hours. The results suggest that a prior ethanol exposure may affect subsequent acute apoptotic cell death induced by ethanol, perhaps by a protective mechanism as the Bcl-2:Bax ratio increases at 24 hours. This study increases our understanding of apoptotic cell death as a consequence of binge drinking during the third trimester equivalent of human foetal development.