Jiadifenolide induces expression of cellular communication network factor (CCN) genes, and CCN2 possesses neurotrophic activity in neuronal precursor cells derived from human induced pluripotent stem cells
Jiadifenolide has been reported to have neurotrophin-like activity in primary rat cortical neurons, and also possesses neurotrophic effects in neuronal precursor cells derived from human induced pluripotent stem cells (hiPSCs), as we have previously reported. However, the molecular mechanisms by which jiadifenolide exerts its neurotrophic effects in rat and human neurons are unknown. Thus, we aimed to investigate the molecular mechanisms and pathways by which jiadifenolide promotes neurotrophic effects. Here, we found that jiadifenolide activated cellular communication network factor (CCN) signaling pathways by up-regulating mRNA level expression of CCN genes in human neuronal cells. We also found that CCN2 (also known as connective tissue growth factor, CTGF) protein promotes neurotrophic effects through activation of the p44/42 mitogen-activated protein kinase (MAPK) signaling pathway. This is the first discovery which connects neurotrophic effects with CCN signaling.
Contributors:Rivera Ana Leonor, Bravo-Martinez Jorge
To determine the dynamical state of the neurons, we have focused on the statistics of the distributions of inter-spike intervals. In particular, we identify two states. The first is the basal state, in which cell spiking follows non-correlated (memory-less) random statistics, usually with a Poisson-like distribution of intervals. The second state is obtained by the activation of the phospholipase C (PLC) signaling cascade with oxotremorine-M (Oxo-M), a M1 receptor agonist, which introduces temporal correlations in the spiking intervals. We interpret these correlations as a shift of the neuronal dynamics towards a critical state. We corroborate that this shift in dynamics is due to a change in the M-channel by applying the specific channel blocker XE991, as well as by blocking the phospholipase C (PLC) with U73122.
Metabolomics and lipidomics data associated with MSCs that have been primed with hypoxia (1% O2) and serum deprivation for 48 hours, as compared to MSC that have been classically cultured (20% FBS, atmospheric oxygen). Data also includes lipidomic and metabolomic data from exosomes derived from primed MSCs