Role of parvalbumin in estrogen protection from ethanol withdrawal syndrome

Background: Parvalbumin (PA) is a calcium-binding protein that has been implicated in protecting neurons from hyperexcitability by sequestering intracellular calcium. This study examined whether ethanol exposure and/or ethanol withdrawal (EW) alter the levels of PA in a manner that is protected by 17 beta-estradiol (E2). Methods: Ovariectomized rats implanted with E2 (EW/E2) or oil pellets (EW/Oil) received chronic ethanol (7.5% w/v, 5 weeks) or control dextrin (Dex/Oil and Dex/E2) diets. At 0 hr, 24 hr, and 2 weeks of EW, three brain areas (the cerebellum, hippocampus, and cortex) were prepared for immunoblotting and immunohistological assessment of PA. Results: At 24 hr of EW, the EW/Oil group showed reduced levels of PA protein and PA-positive neurons in the cerebellum and hippocampus compared with the dextrin control and the EW/E2 groups. At 2 weeks of EW, the reduced levels of PA persisted in the cerebellum but recovered toward the control levels in the hippocampus. The cortex showed no change in PA levels in any of the treatment groups. When tested at 24 hr of EW, the magnitude of EW signs inversely correlated with the levels of PA in the cerebellum and hippocampus. Ethanol exposure itself did not affect PA levels. Conclusion: These data suggest that EW, rather than ethanol exposure, reduces PA levels in a manner that is brain region specific and that is protected by estrogen. Disturbed PA homeostasis is hypothesized to play a role in the hyperexcitability of EW signs.