(915.9) Modulatory role of 17α-estradiol (non-feminizing estrogen) on 6-OHDA-induced Parkinsonism in ovariectomized rats

Poster Board Number: B202

Bikash Medhi (Post Graduate Institute of Medical Education and Research), Seema Bansal (Post Graduate Institute of Medical Education and Research), Amit Sharma (Post Graduate Institute of Medical Education and Research)

Background: Epidemiological studies have reported that the incidence of Parkinson’s disease (PD) is 1.5 times more in men as compared to women. It suggests that gonadal hormones influence the development and progression of PD. Estrogen replacement therapies have a protective effect against dopaminergic toxins and can be protective in Parkinsonism. However, there are multiple unresolved issues regarding the safety of ERT. Thus, there is a essential need to find alternatives that would avoid these health risks.

Objectives: Thus main objective of study was to assess effect of 17α-estradiol, a non-feminizing estrogen, in attenuating PD employing an animal model of surgical menopause. Methodology: 17α-estradiol and 17β-estradiol was injected 10 µg/kg/s.c. for 14 days in ovariectomized 6-OHDA rats. After 14 days of drug administration behavioral parameters of Parkinsonism (sensorimotor activity, motor coordination, and locomotor activity) were performed. These behavioral parameters were further correlated with various biochemical and molecular markers in postmenopausal Parkinsonism. Uterine weight and serum estradiol levels were also assessed to determine estrogenic effect of both the drugs peripherally. Effect of both drugs on expression of ER-α and ER-β in striatum was also evaluated. Further the differential effect of 17α-estradiol and 17β-estradiol was evaluated in postmenopausal Parkinsonism.

Results: 17α-estradiol and 17β-estradiol equally modulated behavioral changes and attenuated rise in oxidative stress markers, inflammatory markers, improving neurotrophic factors and modulation of striatal neuron morphology. 17β-estradiol treatment restored the uterine weight and serum estradiol levels towards normal, however 17α-estradiol did not show any effect on uterine horns and serum estradiol levels. No effect of 17α-estradiol was observed on expression of ER-α and ER-β in the striatum, indicates receptor independent effect of 17α-estradiol

Conclusion: Both 17α-estradiol and 17β-estradiol are equally effective in Parkinsonism, however, 17α-estradiol may prove to be safer alternative of 17β-estradiol in Parkinsonism due to lack of feminizing effect.

Research Associate fellowship no: 45/31/2019/PHA/BMS granted to Seema Bansal by Indian Council of Medical Research (ICMR) New Delhi