Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 95, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2021.107582
Keywords
Simvastatin; Postmenopausal depression; NLRP3; Ovariectomy
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Research demonstrates that SIM can alleviate depressive-like behavior in ovariectomized rats, inhibit microglial activation in the hippocampus, reduce levels of pro-inflammatory mediators, and increase estrogen receptor expression, without significant effects on uterine health.
It is well known that females are more vulnerable than males to stress-related psychiatric disorders, particularly during perimenopausal and postmenopausal periods. Hormone replacement therapy (HRT) has been widely used for the management of postmenopausal depression. However, HRT could be associated with severe adverse effects, including increased risk for coronary heart disease, breast cancer and endometrial cancer. Thus, there is a pressing demand for novel therapeutic options for postmenopausal depression without sacrificing uterine health. Simvastatin (SIM) was proven to have neuroprotective activities besides its hypocholesterolemic effect, the former can be attributed to its, antioxidant, anti-apoptotic and anti-inflammatory activities. Moreover, many reports highlighted that SIM has estrogenic activity and was able to induce the expression of estrogen receptors in rats. The present study showed that SIM (20 mg/kg, p.o.) markedly attenuated depressive-like behavior in ovariectomized (OVX) rats. Moreover, SIM prohibited hippocampal microglial activation, abrogated P2X7 receptor, TLR2 and TLR4 expression, inhibited NLRP3 inflammasome activation, with subsequent reduction in the levels of pro-inflammatory mediators; IL-1 beta and IL-18. Furthermore, a marked elevation in hippocampal expression of ER alpha and ER beta was noted in SIM-treated animals, without any significant effect on uterine relative weight or ER alpha expression. Taken together, SIM could provide a safer alternative for HRT for the management of postmenopausal depression, without any hyperplastic effect on the uterus.
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