Abstract
Loss of endogenous estrogen and dysregulation of the estrogen receptor signaling pathways are associated with an increase in risk for cognitive deficit and depression in women after menopause. Estrogen therapy for menopause increases the risk of breast and ovarian cancers, and stroke. Therefore, it is critical to find an alternate treatment for menopausal women. Osthole (OST), a coumarin, has been reported to have neuroprotective effects. This study examined whether OST improves ovariectomy (OVX)-induced cognitive impairment, and alleviates anxiety- and depression-like behaviors induced by OVX in mice. Adult female C57BL/6J mice were ovariectomized and then treated with OST at a dose of 30 mg/kg for 14 days. At the end of the treatment period, behavioral tests were used to evaluate spatial learning and memory, recognition memory, anxiety- and depression-like behaviors. A cohort of the mice were sacrificed after 14 days of OST treatment and their hippocampi were collected for measurement of the proteins of interest using western blot. OVX-induced alteration in the levels of proteins was accompanied by cognitive deficit, anxiety- and depression-like behaviors. OST treatment improved cognitive deficit, alleviated anxiety- and depression-like behaviors induced by OVX, and reversed OVX-induced alterations in the levels of synaptic proteins and ERα, BDNF, TrKB, p-CREB, p-Akt and Rac1 in the hippocampus. Therefore, reversal of OVX-induced decrease in the levels of hippocampal proteins by OST might contribute to the effects of OST on improving cognitive deficit and alleviating anxiety- and depression-like behaviors induced by OVX.
Highlights
The permanent cessation of menstruation, called menopause or climacteric, is a natural physiological process for women and causes a series of dysfunctions in the autonomic nervous system due to the loss of hormone fluctuation caused by ovarian failure
Our results showed that OST caused an increase in the levels of synaptic proteins including, Kal-7, SYP and GluA1 plus increased levels of brain derived neurotrophic factor (BDNF), tropomyosin kinase B (TrkB), p-cAMP response element binding protein (CREB) and p-protein kinase B (Akt) in the hippocampus of OVX mice
Our results showed that OVX resulted in decreased levels of phosphorylated (p)-CREB, p-AKt, Ras-related C3 botulinum toxin substrate 1 (Rac1), LIM domain kinase 1 (LIMK1) and p-cofilin in the hippocampus of OVX mice, and these decreases were reversed by OST except for LIMK1 and p-cofilin
Summary
The permanent cessation of menstruation, called menopause or climacteric, is a natural physiological process for women and causes a series of dysfunctions in the autonomic nervous system due to the loss of hormone fluctuation caused by ovarian failure. It is often associated with a wide array of neuropsychological symptoms, including cognitive deterioration, anxiety, and depression (Hoga et al, 2015). These psychological disorders exert a negative impact on the quality of life of menopausal women in varying degrees (Jenabi et al, 2015). OST improves impaired spatial learning and memory in a mouse model of Alzheimer’s disease (Yao et al, 2019). These studies suggest that OST is a promising candidate for reversing estrogen deficient-induced alterations in behaviors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
