Back

The smoking cessation drug cytisine requires systemically circulating estrogen for sex-specific neuroprotection in female parkinsonian mice

Zarate, S. M.; Garcia, R. C.; Pandey, G.; Srinivasan, R.

2024-03-27 neuroscience
10.1101/2024.03.21.586192 bioRxiv
Show 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 estrogen mediates this effect, we employ two mouse models aimed at depleting systemically circulating estrogen: (i) bilateral ovariectomy (OVX), and (ii) aromatase inhibition with systemically administered letrozole. In both models, depleting systemically circulating estrogen 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 estrogen 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 Parkinsons disease.

Matching journals

The top 10 journals account for 50% of the predicted probability mass.

1
Scientific Reports
○ 3612 papers in training set
Top 5%
9.0%
Similar papers in this journal
2
Experimental Neurology
○ 61 papers in training set
Top 0.1%
9.0%
Similar papers in this journal
3
Translational Psychiatry
○ 260 papers in training set
Top 1.0%
5.5%
Similar papers in this journal
4
Neurobiology of Disease
○ 148 papers in training set
Top 0.7%
5.2%
Similar papers in this journal
5
The Journal of Neuroscience
● 1025 papers in training set
Top 4%
4.9%
Similar papers in this journal
6
eLife
● 5828 papers in training set
Top 30%
4.1%
7
PLOS ONE
● 5266 papers in training set
Top 35%
3.3%
8
ACS Chemical Neuroscience
● 67 papers in training set
Top 0.3%
3.3%
9
Molecular Psychiatry
○ 282 papers in training set
Top 2%
3.3%
10
Neuropsychopharmacology
○ 153 papers in training set
Top 1%
2.7%
50% of probability mass above
11
Addiction Biology
○ 51 papers in training set
Top 0.4%
2.1%
12
Frontiers in Neuroscience
○ 256 papers in training set
Top 2%
2.1%
13
Brain Research
○ 38 papers in training set
Top 0.2%
1.9%
14
Annals of Neurology
○ 64 papers in training set
Top 0.9%
1.7%
15
The Journal of Pharmacology and Experimental Therapeutics
○ 18 papers in training set
Top 0.2%
1.7%
16
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 31%
1.5%
17
Nature Communications
○ 5641 papers in training set
Top 50%
1.1%
18
npj Parkinson's Disease
○ 105 papers in training set
Top 1%
1.1%
19
Neuropharmacology
○ 68 papers in training set
Top 0.6%
1.1%
20
Molecular Neurobiology
○ 53 papers in training set
Top 0.9%
1.1%
21
Neurotherapeutics
○ 14 papers in training set
Top 0.1%
1.1%
22
Science Advances
● 1243 papers in training set
Top 25%
1.1%
23
The FASEB Journal
○ 194 papers in training set
Top 4%
1.1%
24
Journal of Neuroendocrinology
○ 22 papers in training set
Top 0.2%
1.1%
25
Biological Psychiatry
○ 137 papers in training set
Top 2%
1.1%
26
Movement Disorders
○ 71 papers in training set
Top 0.6%
1.1%
27
Behavioural Brain Research
○ 77 papers in training set
Top 1%
1.1%
28
NeuroToxicology
○ 14 papers in training set
Top 0.2%
1.0%
29
Pharmacological Research
○ 18 papers in training set
Top 0.4%
1.0%
30
Brain Communications
◐ 166 papers in training set
Top 3%
0.9%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.