Chronic Glucocorticoid Exposure Induces Depression-Like Phenotype in Rhesus Macaque (Macaca Mulatta)

It has long been observed in humans that the occurrence of depressive symptoms is often accompanied by the dysfunction of hypothalamic-pituitary-adrenal (HPA) axis. The rodent experiments also showed that chronic corticosterone exposure could induce depression-like phenotype. However, rodents are phylogenetically distant from humans. In contrast, non-human primates bear stronger similarities with humans, suggesting research on primates would provide an important complement. For the first time, we investigated the effects of chronic glucocorticoid exposure on rhesus macaques. Seven male macaques were selected and randomized to glucocorticoid or vehicle groups, which were subjected to either prednisolone acetate or saline injections, respectively. The depression-like behaviors were assessed weekly, and the body weights, HPA axis reactivity, sucrose solution consumption and monoaminergic neurotransmitters were further compared between these two groups. The glucocorticoid group was not found to display more depression-like behaviors than the vehicle group until 7 weeks after treatment. Chronic glucocorticoid exposure significantly decreased the levels of cortisol determined from blood (a biomarker for acute HPA axis reactivity) but increased the hair cortisol concentrations (a reliable indicator of chronic HPA axis reactivity) compared with controls. The glucocorticoid group was also found to consume less sucrose solution than controls, a good manifestation of anhedonia. This could be possibly explained by lower dopamine (DA) levels in cerebrospinal fluid induced by chronic glucocorticoid treatment. The results presented here indicate that chronic glucocorticoid exposure could disturb both the acute and chronic HPA axis reactivity, which eventually disturbed the neurotransmitter system and led monkeys to display depression-like phenotype

Intra-articular injection of ascorbic acid enhances microfracture-mediated cartilage repair

Abstract Previous studies have confirmed that ascorbic acid (AA) can promote cartilage repair and improve cartilage differentiation in bone marrow mesenchymal stem cells. However, the use of microfracture (MFX) combined with AA to repair cartilage damage has not been studied. This study established a rabbit animal model and treated cartilage injury with different concentrations of AA combined with MFX. Macroscopic observations, histological analysis, immunohistochemical analysis and reverse transcription quantitative polymerase chain reaction analysis of TGF-β, AKT/Nrf2, and VEGF mRNA expression were performed. The results showed that intra-articular injection of AA had a positive effect on cartilage repair mediated by microfractures. Moreover, 10 mg/ml AA was the most effective at promoting cartilage repair mediated by microfractures. Intra-articular injection of AA promoted the synthesis of type II collagen and the formation of glycosaminoglycans by downregulating the mRNA expression of TGF-β and VEGF. In summary, this study confirmed that AA could promote cartilage repair after MFX surgery