Curculigoside rescues hippocampal synaptic deficits elicited by PTSD through activating cAMP‐PKA signaling

Abstract

Chronic traumatic stress results in various psychiatric disorders, especially posttraumatic stress disorder (PTSD). Previous study demonstrated that curculigoside (CUR) a component of Rhizoma Curculiginis prevented fear extinction and stress‐induced depression‐like behaviors. However, its effects on PTSD and the mechanisms are still not completely clear. In this study, we observed typical PTSD‐like phenotypes, synaptic deficit, and reduction of BDNF/TrkB signaling pathway in mice receiving modified single prolonged stress and electrical stimulation (SPS&S). By contrast, systemic administration of CUR blocked PTSD‐like phenotypes and synaptic deficits, including reduction of BDNF/TrkB signaling pathway, GluA1 and Arc expression. Importantly, CUR reversed the impairment of PKA signaling pathway elicited by PTSD. We further confirmed that the effects of CUR on synaptic function were through PKA signaling pathway, as H‐89, an inhibitor of PKA blocked the effect of CUR on behavioral changes and BDNF/TrkB signaling pathway. Thereafter, we verified that CUR on synaptic function were through PKA pathway using direct intracerebral injection of CUR and H‐89. Direct intracerebral injection of CUR activated PKA/CREB/BDNF/TrkB, which was blocked by H‐89. Additionally, the docking results showed high binding energies of CUR with A2AR, AC, PRKACA, and PRKAR1A, which might indicate that CUR functions through regulating PKA signaling pathway. In conclusion, CUR prevented the behavioral changes and hippocampal synaptic deficits elicited by PTSD through activating cAMP‐PKA signaling.

Overexpression of olfactory receptor 78 ameliorates brain injury in cerebral ischaemia–reperfusion rats by activating Prkaca‐mediated cAMP/PKA‐MAPK pathway

“…60 Meanwhile, activation of the cAMP-PKA signalling pathway has been found to rescue hippocampal synaptic defects caused by posttraumatic stress disorder (PTSD). 61 In this study, we found that Prkaca was markedly downregulated in OGD/R-induced neurons and MCAO/R rats.…”

“… 60 Meanwhile, activation of the cAMP‐PKA signalling pathway has been found to rescue hippocampal synaptic defects caused by posttraumatic stress disorder (PTSD). 61 In this study, we found that Prkaca was markedly downregulated in OGD/R‐induced neurons and MCAO/R rats. Overexpression of Prkaca reduced secretion of inflammatory factors and inhibited OGD/R‐induced Ca 2+ overload and neuronal apoptosis through activating the cAMP/PKA‐MAPK signalling pathway.…”

“…Moreover, a report has showed that the expression of Prkaca enhances the intensity of the PKA‐RCA1 signal transmission, which contributes to the development of neurons and the formation of dendritic spines 60 . Meanwhile, activation of the cAMP‐PKA signalling pathway has been found to rescue hippocampal synaptic defects caused by posttraumatic stress disorder (PTSD) 61 . In this study, we found that Prkaca was markedly downregulated in OGD/R‐induced neurons and MCAO/R rats.…”

Hippocampal Proteomics Reveals the Role of Glutamatergic Synapse Activation in the Depression Induced by Perfluorooctane Sulfonate

“…Among them, many researchers show high concern about CREB/BDNF/TrkB signaling in depression. Through the same signaling pathway, these studies provide many meaningful ideas for the exploration of depression like myelination, hippocampal synaptic plasticity, and G protein-coupled receptor 39, − which have something in common with our research.…”

Systems biology approaches to identify potential targets and inhibitors of the intestinal microbiota to treat depression

“…In antidepressant drug treatment, most drugs are metabolized via the polymorphic cytochrome P450 enzyme CYP2D6 55 . Activating cAMP-PKA signaling could prevent the behavioral changes and hippocampal synaptic deficits elicited by posttraumatic stress disorder (PTSD) 56 . Restoring hippocampal cAMP and BDNF levels could be an antidepressant treatment 57 .…”