Activation of EphB2 in the basolateral amygdala promotes stress vulnerability of mice by increasing NMDA-dependent synaptic function.

The occurrence of major depressive disorder (MDD) has been linked to an increased vulnerability to stress. The basolateral amygdala (BLA) is one of the critical brain areas that involved in the regulation of pathological reactivity to stress. Increasing evidence indicates that the EphB2 receptor (EphB2) plays a critical role in neuropsychiatric disorders, such as Alzheimer's disease, pain and anxiety.

Dorsal raphe projection inhibits the excitatory inputs on lateral habenula and alleviates depressive behaviors in rats.

Hypofunction of the serotonergic (5-HT) system has close relationship with the symptoms in major depressive disorders (MDD), however, the underlying neural circuitry mechanisms are not fully understood. Lateral habenula (LHb) plays a crucial role in aversive behaviors and is activated in conditions of depression. It has been reported that 5-HT inhibits the excitability of LHb neurons, leading to the hypothesis that decreased transmission of 5-HT would elevate the activity of LHb and therefore mediates depressive symptoms.

Defective CFTR leads to aberrant β-catenin activation and kidney fibrosis.

Cystic fibrosis transmembrane conductance regulator (CFTR), known as a cAMP-activated Cl channel, is widely expressed at the apical membrane of epithelial cells in a wide variety of tissues. Of note, despite the abundant expression of CFTR in mammalian kidney, the role of CFTR in kidney disease development is unclear. Here, we report that CFTR expression is downregulated in the UUO (unilateral ureteral obstruction)-induced kidney fibrosis mouse model and human fibrotic kidneys.

Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs.

The success of stem cell-mediated gene therapy in cancer treatment largely depends on the specific homing ability of stem cells. We have previously demonstrated that after in vitro induction of neuronal differentiation and dedifferentiation, bone marrow stromal cells (BMSCs) revert to a primitive stem cell population (De-neu-BMSCs) distinct from naive BMSCs. We report here that De-neu-BMSCs express significantly higher levels of chemokines, and display enhanced homing abilities to glioma, the effect of which is mediated by the activated CCL5/CCR1/ERK axis.

Aquaporin-4 deficiency facilitates fear memory extinction in the hippocampus through excessive activation of extrasynaptic GluN2B-containing NMDA receptors.

Aquaporin-4 (AQP-4) is the predominant water channel in the brain and primarily expressed in astrocytes. Astrocytes have been generally believed to play important roles in regulating synaptic plasticity and information processing. A growing number of evidence shows that AQP-4 plays a potential role in the regulation of astrocyte function.

CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis.

While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues.

Defective CFTR- β-catenin interaction promotes NF-κB nuclear translocation and intestinal inflammation in cystic fibrosis.

While inflammation with aberrant activation of NF-κB pathway is a hallmark of cystic fibrosis (CF), the molecular mechanisms underlying the link between CFTR defect and activation of NF-κB-mediated pro-inflammatory response remain elusive. Here, we investigated the link between CFTR defect and NF-κB activation in ΔF508cftr-/- mouse intestine and human intestinal epithelial cell lines. Our results show that the NF-κB/COX-2/PGE2 pathway is activated whereas the β-catenin pathway is suppressed in CF mouse intestine and CFTR-knockdown cells.

MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells.

The biologic studies of human neural crest stem cells (hNCSCs) are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs).

Propranolol decreases retention of fear memory by modulating the stability of surface glutamate receptor GluA1 subunits in the lateral amygdala.

Background And Purpose: Posttraumatic stress disorder (PTSD) is a mental disorder with enhanced retention of fear memory and has profound impact on quality of life for millions of people worldwide. The β-adrenoceptor antagonist propranolol has been used in preclinical and clinical studies for the treatment of PTSD, but the mechanisms underlying its potential efficacy on fear memory retention remain to be elucidated.

Experimental Approach: We investigated the action of propranolol on the retention of conditioned fear memory, the surface expression of glutamate receptor GluA1 subunits of AMPA receptors and synaptic adaptation in the lateral amygdala (LA) of rats.

Calcitonin gene-related peptide erases the fear memory and facilitates long-term potentiation in the central nucleus of the amygdala in rats.

Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide, which plays a critical role in the central nervous system. CGRP binds to G protein-coupled receptors, including CGRP1, which couples positively to adenylyl cyclase (AC) and protein kinase A (PKA) activation. CGRP and CGRP1 receptors are enriched in central nucleus of the amygdala (CeA), the main part of the amygdala, which regulates conditioned fear memories.

The cystic fibrosis transmembrane conductance regulator as a biomarker in non-small cell lung cancer.

An increased risk of non-small cell lung cancer (NSCLC) in cystic fibrosis (CF) patients and carriers of CF transmembrane conductance regulator (CFTR) mutations has been proposed. However, the role of CFTR in lung cancer remains controversial. In the present study, CFTR expression was assessed in 165 NSCLC tumors and 22 normal lung samples with validation in an independent series of 131 samples.

Regulation of emotional memory by hydrogen sulfide: role of GluN2B-containing NMDA receptor in the amygdala.

As an endogenous gaseous molecule, hydrogen sulfide (H2 S) has attracted extensive attention because of its multiple biological effects. However, the effect of H2 S on amygdala-mediated emotional memory has not been elucidated. Here, by employing Pavlovian fear conditioning, an animal model widely used to explore the neural substrates of emotion, we determined whether H2 S could regulate emotional memory.

Aggravation of seizure-like events by hydrogen sulfide: involvement of multiple targets that control neuronal excitability.

Aims: Epileptic seizures are well-known neurological complications following stroke, occurring in 3% of patients. However, the intrinsic correlation of seizures with stroke remains largely unknown. Hydrogen sulfide (H2 S) is a gas transmitter that may mediate cerebral ischemic injury.

Disrupted interaction between CFTR and AF-6/afadin aggravates malignant phenotypes of colon cancer.

How mutations or dysfunction of CFTR may increase the risk of malignancies in various tissues remains an open question. Here we report the interaction between CFTR and an adherens junction molecule, AF-6/afadin, and its involvement in the development of colon cancer. We have found that CFTR and AF-6/afadin are co-localized at the cell-cell contacts and physically interact with each other in colon cancer cell lines.

Downregulation of CFTR promotes epithelial-to-mesenchymal transition and is associated with poor prognosis of breast cancer.

The epithelial-to-mesenchymal transition (EMT), a process involving the breakdown of cell-cell junctions and loss of epithelial polarity, is closely related to cancer development and metastatic progression. While the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl(-) and HCO3(-) conducting anion channel expressed in a wide variety of epithelial cells, has been implicated in the regulation of epithelial polarity, the exact role of CFTR in the pathogenesis of cancer and its possible involvement in EMT process have not been elucidated. Here we report that interfering with CFTR function either by its specific inhibitor or lentiviral miRNA-mediated knockdown mimics TGF-β1-induced EMT and enhances cell migration and invasion in MCF-7.

Ion channels/transporters as epigenetic regulators? -a microRNA perspective.

MicroRNA (miRNA) alterations in response to changes in an extracellular microenvironment have been observed and considered as one of the major mechanisms for epigenetic modifications of the cell. While enormous efforts have been made in the understanding of the role of miRNAs in regulating cellular responses to the microenvironment, the mechanistic insight into how extracellular signals can be transduced into miRNA alterations in cells is still lacking. Interestingly, recent studies have shown that ion channels/transporters, which are known to conduct or transport ions across the cell membrane, also exhibit changes in levels of expression and activities in response to changes of extracellular microenvironment.