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 17beta-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.


CONCLUSIONS
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.
Rewal
Mridula
M
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas 76107-2699, USA. mrewal@hsc.unt.edu
Wen
Yi
Y
Wilson
Andrew
A
Simpkins
James W
JW
Jung
Marianna E
ME
D000818:Animals; D001835:Body Weight / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000097:blood; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004032:Diet; D004958:Estradiol / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects* / Q000097:blood; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D010052:Ovariectomy; D010320:Parvalbumins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
D002492:Central Nervous System Depressants; D010320:Parvalbumins; D000431:Ethanol; D004958:Estradiol