Systemically circulating 17β-estradiol enhances the neuroprotective effect of the smoking cessation drug cytisine in female parkinsonian mice

Bibliographic Details
Title: Systemically circulating 17β-estradiol enhances the neuroprotective effect of the smoking cessation drug cytisine in female parkinsonian mice
Authors: Sara M. Zarate, Roger C. Garcia, Gauri Pandey, Rahul Srinivasan
Source: npj Parkinson's Disease, Vol 11, Iss 1, Pp 1-10 (2025)
Publisher Information: Nature Portfolio, 2025.
Publication Year: 2025
Collection: LCC:Neurology. Diseases of the nervous system
Subject Terms: Neurology. Diseases of the nervous system, RC346-429
More Details: Abstract The smoking cessation drug cytisine exerts neuroprotection in substantia nigra pars compacta (SNc) dopaminergic (DA) neurons of female but not male 6-hydroxydopamine (6-OHDA) lesioned parkinsonian mice. To address the important question of whether circulating 17β−estradiol mediates this effect, we employ two mouse models aimed at depleting systemically circulating 17β-estradiol: (i) bilateral ovariectomy (OVX), and (ii) aromatase inhibition with systemically administered letrozole. In both models, depleting systemically circulating 17β-estradiol in female 6-OHDA lesioned parkinsonian mice results in the loss of cytisine-mediated neuroprotection as measured using apomorphine-induced contralateral rotations and SNc DA neurodegeneration. Our experiments also reveal that OVX alone exerts neuroprotection in SNc DA neurons due to compensatory changes not observed in the letrozole model, which underscores the importance of using independent models of 17β-estradiol depletion to study neuroprotection. Taken together, our findings suggest that the smoking cessation drug cytisine is a viable neuroprotective drug for pre-menopausal women with Parkinson’s disease.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2373-8057
Relation: https://doaj.org/toc/2373-8057
DOI: 10.1038/s41531-024-00855-3
Access URL: https://doaj.org/article/8a055b41420b4841b5d4aef36c6267ac
Accession Number: edsdoj.8a055b41420b4841b5d4aef36c6267ac
Database: Directory of Open Access Journals
More Details
ISSN:23738057
DOI:10.1038/s41531-024-00855-3
Published in:npj Parkinson's Disease
Language:English