Astragaloside IV inhibits astrocyte senescence: implication in Parkinson's disease.

BACKGROUND: Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson's disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge and exerts anti-inflammatory and longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. METHODS: Long culture-induced replicative senescence model and lipopolysaccharide/1-methyl-4-phenylpyridinium (LPS/MPP+)-induced premature senescence model and a mouse model of PD were used to investigate the effect of AS-IV on astrocyte senescence in vivo and in vitro. Immunocytochemistry, qPCR, subcellular fractionation, flow cytometric analyses, and immunohistochemistry were subsequently conducted to determine the effects of AS-IV on senescence markers. RESULTS: We found that AS-IV inhibited the astrocyte replicative senescence and LPS/MPP+-induced premature senescence, evidenced by decreased senescence-associated ß-galactosidase activity and expression of senescence marker p16, and increased nuclear level of lamin B1, and reduced pro-inflammatory senescence-associated secretory phenotype. More importantly, we showed that AS-IV protected against the loss of dopamine neurons and behavioral deficits in the mouse model of PD, which companied by reduced accumulation of senescent astrocytes in substantia nigra compacta. Mechanistically, AS-IV promoted mitophagy, which reduced damaged mitochondria accumulation and mitochondrial reactive oxygen species generation and then contributed to the suppression of astrocyte senescence. The inhibition of autophagy abolished the suppressive effects of AS-IV on astrocyte senescence. CONCLUSIONS: Our findings reveal that AS-IV prevents dopaminergic neurodegeneration in PD via inhibition of astrocyte senescence through promoting mitophagy and suggest that AS-IV is a promising therapeutic strategy for the treatment of age-associated neurodegenerative diseases such as PD.

α-Synuclein disrupts the anti-inflammatory role of Drd2 via interfering ß-arrestin2-TAB1 interaction in astrocytes.

BACKGROUND: α-Synuclein (α-Syn)-induced neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Dopamine D2 receptor (Drd2) has been regarded as a potential anti-inflammatory target in the therapy of neurodegenerative diseases. However, the effect of astrocytic Drd2 in α-Syn-induced neuroinflammation remains unclear. METHODS: The effect of Drd2 on neuroinflammation was examined in mouse primary astrocyte in vitro and A53T transgenic mice in vivo. The inflammatory responses of astrocyte were detected using immunofluorescence, ELISA, and qRT-PCR. The details of molecular mechanism were assessed using Western blotting and protein-protein interaction assays. RESULTS: We showed that the selective Drd2 agonist quinpirole suppressed inflammation in the midbrain of wild-type mice, but not in α-Syn-overexpressed mice. We also found that Drd2 agonists significantly alleviated LPS-induced inflammatory response in astrocytes, but failed to suppress α-Syn-induced inflammatory response. The anti-inflammation effect of Drd2 was dependent on ß-arrestin2-mediated signaling, but not classical G protein pathway. α-Syn reduced the expression of ß-arrestin2 in astrocytes. Increased the ß-arrestin2 expression restored in the anti-inflammation of Drd2 in α-Syn-induced inflammation. Furthermore, we demonstrated that α-Syn disrupted the anti-inflammation of Drd2 via inhibiting the association of ß-arrestin2 with transforming growth factor-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and promoting TAK1-TAB1 interaction in astrocytes. CONCLUSIONS: Our study illustrates that astrocytic Drd2 inhibits neuroinflammation through a ß-arrestin2-dependent mechanism and provides a new strategy for treatment of PD. Our findings also reveal that α-Syn disrupts the function of ß-arrestin2 and inflammatory pathways in the pathogenesis of PD.

Readiness for Hospital Discharge After a Cesarean Section and Associated Factors Among Chinese Mothers: A Single Centre Cross-Sectional Study.

Purpose: Knowledge of the readiness for hospital discharge can help health care professionals accurately determine the patients' discharge time. However, few studies were on the readiness for discharge and its related factors among mothers with cesarean sections. Thus, this study aims to examine the readiness for hospital discharge and its associated factors among Chinese mothers with cesarean sections. Patients and Methods: A single-centre cross-sectional study was conducted from September 2020 to March 2021 in Guangzhou, China. Three hundred thirty-nine mothers with cesarean sections completed the questionnaires on demographic and obstetric characteristics, readiness for hospital discharge, quality for discharge teaching, parenting sense of competence, family function, and social support. Multiple linear regression analysis was used to identify independent factors influencing readiness for hospital discharge among mothers with cesarean sections. Results: The total score of readiness for hospital discharge was 136.47 ± 25.29. The quality of discharge teaching, parenting sense of competence, number of cesareans, family function, and attending antenatal classes were independent factors influencing the readiness for hospital discharge (P < 0.05) among mothers with cesarean sections. Conclusion: The readiness for hospital discharge of mothers with cesarean sections need to be improved. Improving the quality of discharge teaching, parenting sense of competence, and family function may help improve the readiness for hospital discharge of mothers with cesarean sections.