Highlights d The PVT/CeA pathway associates opiate reward to the environment d Manipulation of the PVT/NAc or NAc/LH pathway prevents opiate-primed relapse d Repeated opiate use enhances feedforward inhibition from PVT to the NAc/LH pathway d iDISCO + mapping reveals brain-wide networks for storing opiate-associated memories
Synaptic spine loss is one of the major preceding consequences of stroke damages, but its underlying molecular mechanisms remain unknown. Here, we report that a direct interaction of DAPK1 with Tau causes spine loss and subsequently neuronal death in a mouse model with stroke. We found that DAPK1 phosphorylates Tau protein at Ser262 (pS262) in cortical neurons of stroke mice. Either genetic deletion of DAPK1 kinase domain (KD) in mice (DAPK1-KD−/−) or blocking DAPK1-Tau interaction by systematic application of a membrane permeable peptide protects spine damages and improves neurological functions against stroke insults. Thus, disruption of DAPK1-Tau interaction is a promising strategy in clinical management of stroke.
In the present study, the tumor-suppressive role of microRNA-127-3p (miR-127-3p) in epithelial ovarian cancer (EOC) was elucidated. Expression of miR-127-3p was examined by quantitative RT-PCR (qRT-PCR) in 9 EOC cell lines and clinical samples from 13 EOC patients. EOC cell lines, OVCAR-3 and Caov-3, were transduced with a lentivirus to overexpress endogenous miR-127-3p. The tumor-suppressive effects of miR-127-3p on EOC proliferation, bufalin sensitivity, invasion and in vivo growth were investigated through proliferation, bufalin sensitivity wound-closure and in vivo tumorigenicity assays, respectively. In addition, luciferase reporter assay and qRT-PCR were conducted to verify whether the Bcl-2-associated athanogene 5 (BAG5) gene was the downstream target of miR-127-3p in EOC. BAG5 was subsequently upregulated in the OVCAR-3 and Caov-3 cells to examine its functional correlation with miR‑127-3p regulation in EOC. The results revealed that in both EOC cell lines and EOC tumor tissues, miR-127-3p was downregulated. Lentiviral-mediated miR-127-3p overexpression exerted tumor-suppressive effects in OVCAR-3 and Caov-3 cells by reducing in vitro proliferation and invasion, increasing bufalin sensitivity, and inhibiting in vivo tumor growth. miR‑127-3p directly regulated the BAG5 gene in EOC. Subsequent BAG5 upregulation ameliorated the tumor-suppressive effects of miR-127-3p overexpression in EOC. In conclusion, miR-127-3p functions as a tumor suppressor in EOC, and its influence on EOC is directly through regulation of BAG5.
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