BACKGROUND AND OBJECTIVE: Impaired learning and memory are the complications of Parkinson's disease. Moreover, estrogen reduction during menopause may impair memory. Given that genistein has neuroprotective and estrogen effects, this study aimed to investigate the effect of genistein on learning and memory of ovariectomized rat model of Parkinson’s disease.

METHODS: In this experimental study, 48 female Wistar rats were divided into six groups of eight, including a Parkinsonism group receiving dimethyl sulfoxide solvent, four ovariectomized groups of rats with Parkinson’s disease receiving dimethyl sulfoxide solvent, genistein (10 mg/kg), tamoxifen (20 mg/kg), and a mixture of genistein (10 mg/kg) and tamoxifen (20 mg/kg) as pre-treatment for a week, as well as a control group. Nigrostriatal pathway was destroyed by 8 µg of 6-hydroxy-dopamine. Learning and spatial memory were evaluated by Morris water maze test.

FINDINGS: In training and assessment stages, there was a significant difference between the control group and the Parkinsonism and ovariectomized-Parkinsonism groups (p<0.0001). The mean times the ovariectomized-Parkinsonism and Parkinsonism groups remained in the target quadrant were 4.21±0.26 s and 5.94±0.61 s, respectively, which was less compared to the control group (12.15±0.33). In addition, ovariectomy prolonged acquisition (p=0.002) and reduced probe testing time (p=0.034) in the rats with Parkinson's disease. The genistein group spent more time in the target quadrant compared to the group receiving genistein and tamoxifen (11.85±0.46 s vs. 6.37±0.86 s, respectively; p=0.0001).

CONCLUSION: The results showed that genistein improves spatial learning and memory in the ovariectomized rat model of Parkinson’s disease.