TY - JOUR
T1 - In vitro effects of ethanol withdrawal and spermidine on viability of hippocampus from male and female rat
AU - Prendergast, Mark A.
AU - Harris, Barton R.
AU - Blanchard, John A.
AU - Mayer, Sveta
AU - Alex Gibson, D.
AU - Littleton, John M.
PY - 2000
Y1 - 2000
N2 - Background: Long-term ethanol dependence results in neuronal adaptation that likely contributes to ethanol withdrawal-induced central nervous system excitability and, potentially, neurotoxicity. This has been suggested to result, in part, from increased release of or response to endogenous polyamines. Furthermore, it has been reported that neurological difficulties related to ethanol dependence and withdrawal may be more severe in female than in male alcoholics. Thus, we designed this study to examine effects of the polyamine spermidine on neurotoxicity associated with withdrawal from long-term ethanol exposure by using organotypic hippocampal slice cultures derived from male and female rats. Methods and Results: Twenty-four hours of withdrawal after continuous 10 day ethanol exposure (100 mM in culture medium) resulted in cytotoxicity in hippocampal slice explants obtained from both sexes. This was most evident in pyramidal cell layers of the CA1 region, and no sex differences were observed in the severity of damage. Exposure of explants from both sexes to the NMDA blocker MK-801 during ethanol withdrawal significantly reduced this toxicity. In control cultures, exposure to spermidine (100 μM) alone produced significant and similar cytotoxicity in hippocampal explants of male and female rats. Exposure to spermidine (100 μM) during ethanol withdrawal significantly increased cytotoxicity in all regions of explants. In the CA3 region, spermidine-potentiation of ethanol withdrawal damage was significantly greater in explants from female rats compared with those from male rats. Conclusions: These data demonstrate the presence of significant hippocampal neurotoxicity during withdrawal from long-term ethanol exposure that is mediated, in part, by overactivation of NMDA receptors. Furthermore, these findings suggest that the central nervous system of females may be more susceptible than that of males to polyamine-mediated neuronal damage during withdrawal from long-term ethanol exposure.
AB - Background: Long-term ethanol dependence results in neuronal adaptation that likely contributes to ethanol withdrawal-induced central nervous system excitability and, potentially, neurotoxicity. This has been suggested to result, in part, from increased release of or response to endogenous polyamines. Furthermore, it has been reported that neurological difficulties related to ethanol dependence and withdrawal may be more severe in female than in male alcoholics. Thus, we designed this study to examine effects of the polyamine spermidine on neurotoxicity associated with withdrawal from long-term ethanol exposure by using organotypic hippocampal slice cultures derived from male and female rats. Methods and Results: Twenty-four hours of withdrawal after continuous 10 day ethanol exposure (100 mM in culture medium) resulted in cytotoxicity in hippocampal slice explants obtained from both sexes. This was most evident in pyramidal cell layers of the CA1 region, and no sex differences were observed in the severity of damage. Exposure of explants from both sexes to the NMDA blocker MK-801 during ethanol withdrawal significantly reduced this toxicity. In control cultures, exposure to spermidine (100 μM) alone produced significant and similar cytotoxicity in hippocampal explants of male and female rats. Exposure to spermidine (100 μM) during ethanol withdrawal significantly increased cytotoxicity in all regions of explants. In the CA3 region, spermidine-potentiation of ethanol withdrawal damage was significantly greater in explants from female rats compared with those from male rats. Conclusions: These data demonstrate the presence of significant hippocampal neurotoxicity during withdrawal from long-term ethanol exposure that is mediated, in part, by overactivation of NMDA receptors. Furthermore, these findings suggest that the central nervous system of females may be more susceptible than that of males to polyamine-mediated neuronal damage during withdrawal from long-term ethanol exposure.
KW - Cell Culture
KW - Ethanol
KW - NMDA
KW - Neurotoxicity
KW - Sex
KW - Spermidine
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U2 - 10.1111/j.1530-0277.2000.tb01990.x
DO - 10.1111/j.1530-0277.2000.tb01990.x
M3 - Article
C2 - 11141045
AN - SCOPUS:0034538589
SN - 0145-6008
VL - 24
SP - 1855
EP - 1861
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
IS - 12
ER -