An estimated 20% of women experience depression at some point during menopause. Hormone replacement therapy (HRT), as the main therapy for depression and other menopausal syndromes, comes with a few undesirable side effects and a potential increase in cancer and cardiovascular risk. Consequently, there is a dire need for the development of new therapies to treat menopausal depression. Oxidative stress combined with the decline in sex hormones might explain the occurrence of psychological symptoms characteristic of menopause. Therefore, antioxidants have been suggested as a promising therapy for aging-associated diseases, such as menopausal depression. As a flavonoid antioxidant, kaempferol might have a potential neuroprotective action. Hence, the study was conducted to assess the potential antidepressant action of kaempferol and clarify the underlying mechanism. The results show that kaempferol has potential beneficial effects on VCD-induced rodent model of menopausal depression and produces antioxidant effects as well as increases the deacetylation of superoxide dismutase 2 (SOD2) and the protein level of Sirtuin3 (Sirt3) in the hippocampus. On the contrary, Sirt3 depletion abrogated the antidepressant- and anxiolytic-like effects as well as antioxidant effects of kaempferol. In conclusion, kaempferol might produce antidepressant effects via upregulating the expression of Sirt3, the major deacetylase in mitochondria, and subsequently activate the mitochondrial antioxidases. These findings shed some light on the use of kaempferol or vegetables and herbs that contain kaempferol as a complementary therapy for menopausal depression.

Depression is one very common mental health disorder which can cause morbidity and mortality if not addressed. Recent studies have provided strong evidence that depression may be accompanied by immune activation, secondary inflammatory reaction, and hyperactivity of the Hypothalamic Pituitary Adrenal (HPA) axis. It is well-known that it takes at least 2 weeks for conventional antidepressants, especially SSRIs (Selective serotonin reuptake inhibitors) to produce effects. To better understand the mechanism of antidepressant effects on depression and subsequently further elucidate the pathogenesis of depression, we selected phytestrogen daidzein (DD) to observe its effects on the depression-like and anxiety-like behavior in two different rodent models of depression which were induced by learned helplessness and chronic mild stress (CMS) and then simultaneous evaluation of the depression-like behavior, the activity of HPA axis, and circulatory cytokines. Our results showed that daidzein attenuated depression-like behaviors through alleviating HPA axis hyperactivity, decreasing the levels of stress-related hormones, and partly rectifying some inflammatory cytokines imbalance in both the rodent models of depression.

Cerebral palsy (CP)，as a neurodevelopmental disorder, usually occurs early in life and persists throughout the whole life. Several risk factors, including perinatal hypoxia-ischemia (HI), may contribute to occurrence of CP in preterm infants. DNA hydroxymethylation has been shown to play an important role in neurodevelopment and neurodegenerative disorders. However, the effect of DNA hydroxymethylation in cerebral palsy remains unknown. The aim of this study is to explore whether and how DNA hydroxymethylation is involved in cerebral palsy pathogenesis. We observed that overall 5-hydroxymethylcytosine (5hmC) abundance in the cortex of the temporal lobe of rat pups was decreased significantly after hypoxic-ischemic injury and the reduced expression of Tet1 and Tet2 enzymes might be responsible for this change. It is well-known that identified differential hydroxymethylation regions (DhMRs) are richly involved in multiple signaling pathways related to neuronal development and function. Hence, we also found that reduced 5hmC modification on the DhMRs-related genes were accompanied by the decrease of their mRNA expression levels. These results suggest that 5hmC modification is possibly involved in the pathogenesis of cerebral palsy and may potentially serve as a new therapeutic target.

Cerebral palsy (CP) is a severe cerebral disease with high mortality and morbidity, which leads to great challenges for the suffering children and their families. Hence, the need for the efficacious and safe treatments is urgent. As a physical therapy arising from traditional Chinese medicine (TCM), Tuina has shown multiple effects on various diseases, including cerebral palsy. Nevertheless, the detailed mechanisms of Tuina on CP remain unknown, which impedes its further clinical application. Herein, we explored the effects of Tuina on CP and its potential mechanisms. Thirty Sprague Dawley (SD) male rats were randomly divided into sham, model, and Tuina groups (model + Tuina). CP rat model was established by hypoxia-ischemia via permanent occlusion of left common carotid artery and hypoxia for 2.5 hours caused by anaerobic environment, which was subsequently followed by onset of Tuina treatment from postnatal day 7 (P7) to P49. After completion of Tuina treatment, the behavioral tests showed that Tuina treatment not only improved the retarded body weight and impaired motor balance function, but also ameliorated weakened learning and memory function of CP rats. Moreover, immunohistochemistry and western blot also revealed a reduced expression of NLRP3 inflammasome and corresponding pyroptosis-related molecules induced by NLRP3 in CP rats after Tuina treatment. Therefore, our study indicated that Tuina treatment may improve impaired neurocognitive function of CP rats, which was possibly realised via inhibiting NLRP3-induced pyroptosis.