Related Experiment Video
Updated: Sep 23, 2025
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Targeting the TLR4/NF-κΒ Axis and NLRP1/3 Inflammasomes by Rosuvastatin: A Role in Impeding Ovariectomy-Induced
Muhammed A Saad1,2, Muhammad Y Al-Shorbagy3,4, Hany H Arab5
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Abstract:
Postmenopausal hormone-related cognitive decline has gained an immense interest to explore the underlying mechanisms and potential therapies. The current work aimed to study the possible beneficial effect of rosuvastatin (ROS) on the cognitive decline induced by ovariectomy in rats. Four groups were used as follows: control group, control + rosuvastatin, ovariectomy, and ovariectomy + rosuvastatin. After sham operation or ovariectomy, rats were given saline or oral dosages of ROS (2 mg/kg) every day for 30 days. The cognitive functions were assessed using the Morris water maze paradigm, Y-maze test, and new object recognition test. After rat killing, TLR4, caspase-8, and NLRP mRNA expression and protein levels of ASC, AIM2, caspase-1, NLRP1, and PKR were measured in hippocampus. This was complemented by the estimation of tissue content of NF-κΒ, IL-1β, and IL-18 and serum lipid profile quantification. Rosuvastatin showed a promising potential for halting the cognitive impairments induced by estrogen decline through interfering with the TLR4/NF-κΒ/NLRP1/3 axis and inflammasomes activation and the subsequent pyroptosis. This was complemented by the amendment in the deranged lipid profile. Rosuvastatin may exert a beneficial role in attenuating the inflammatory and apoptotic signaling mechanisms associated with postmenopausal cognitive decline. Further investigations are needed to unveil the relationship between deranged plasma lipids and cognitive function.
Insights
Rosuvastatin may help prevent cognitive decline after menopause by reducing inflammation and apoptosis. This study explored its effects on ovariectomized rats, showing promising results for brain health.
Area of Science:
- Neuroscience
- Pharmacology
- Endocrinology
Background:
- Postmenopausal hormone decline is linked to cognitive impairment.
- Understanding the mechanisms and finding therapies for this decline is crucial.
Purpose of the Study:
- To investigate the potential benefits of rosuvastatin in mitigating ovariectomy-induced cognitive decline in rats.
- To explore the underlying molecular pathways affected by rosuvastatin.
Main Methods:
- Ovariectomized rats were treated with rosuvastatin (2 mg/kg) daily for 30 days.
- Cognitive functions were assessed using behavioral tests (Morris water maze, Y-maze, new object recognition).
- Hippocampal and serum markers related to inflammation, apoptosis, and lipid profiles were analyzed.
Main Results:
- Rosuvastatin treatment improved cognitive functions in ovariectomized rats.
- It modulated the TLR4/NF-κB/NLRP1/3 axis, reduced inflammasome activation, and pyroptosis.
- Lipid profiles were improved, and inflammatory markers (IL-1β, IL-18) were reduced.
Conclusions:
- Rosuvastatin shows potential in preventing estrogen decline-induced cognitive impairments.
- It acts by inhibiting inflammatory and apoptotic signaling pathways.
- Further research is needed to clarify the link between lipid profiles and cognitive function.
