Estrogen protects against 3-methylindole-induced olfactory loss

Olfactory dysfunction is among the first signs of Alzheimer's disease (AD). Since estrogen therapy may mitigate the cognitive symptoms of AD, we determined whether 17beta-estradiol (E2) alters the olfactory discrimination performance of female rats exposed to the olfactotoxicant 3-methylindole (3-MI). Twelve ovariectomized rats received daily injections of E2 (1 mg/kg i.p.) in corn oil and 10 received daily injections of corn oil alone. Sensory testing occurred on a near-daily basis throughout a 10-week test period, midway in which a single injection of 3-MI was administered (300 mg/kg i.p.). On each pre- and post-3-MI test day, the rats were required to perform a series of successively more difficult odor discrimination tasks until one was reached where <80% performance was attained. The tasks were between the odor of a 10-4 v/v concentration of ethyl acetate (EA) and the odor of each of six different concentrations of butanol added to the EA (10-4, 10-4.5, 10-5.0, 10-5.5, 10-6.0, 10-6.5 v/v). Following 3-MI treatment, the performance of the E2-treated rats was found to be superior to that of the oil-treated rats and to return more quickly to the pre-3 MI baseline, suggesting that high doses of E2 mitigate 3-MI-induced smell loss in rats. Additional work is needed to determine the physiologic basis of this phenomenon.