GABA(δ) receptor hypofunction in the amygdala-hippocampal circuit underlies stress-induced anxiety.

Dysregulated GABAergic inhibition in the amygdala has long been implicated in stress-related neuropsychiatric disorders. However, the molecular and circuit mechanisms underlying the dysregulation remain elusive. Here, by using a mouse model of chronic social defeat stress (CSDS), we observed that the dysregulation varied drastically across individual projection neurons (PNs) in the basolateral amygdala (BLA), one of the kernel amygdala subregions critical for stress coping.

Prefrontal GABA(δ)R Promotes Fear Extinction through Enabling the Plastic Regulation of Neuronal Intrinsic Excitability.

Extinguishing the previously acquired fear is critical for the adaptation of an organism to the ever-changing environment, a process requiring the engagement of GABA receptors (GABARs). GABARs consist of tens of structurally, pharmacologically, and functionally heterogeneous subtypes. However, the specific roles of these subtypes in fear extinction remain largely unexplored.

Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety.

Dysregulated prefrontal control over amygdala is engaged in the pathogenesis of psychiatric diseases including depression and anxiety disorders. Here we show that, in a rodent anxiety model induced by chronic restraint stress (CRS), the dysregulation occurs in basolateral amygdala projection neurons receiving mono-directional inputs from dorsomedial prefrontal cortex (dmPFC→BLA PNs) rather than those reciprocally connected with dmPFC (dmPFC↔BLA PNs). Specifically, CRS shifts the dmPFC-driven excitatory-inhibitory balance towards excitation in the former, but not latter population.

Gender-dependent regulation of anxiety-like behavior by δ subunit-containing GABAA receptor during postnatal development.

The δ subunit-containing GABAA receptor [GABAA(δ)R], which is exclusively situated in the extrasynaptic space, has considerable influence on emotion and behavior. Although the expression of this receptor experiences dramatic fluctuation during postnatal development, it remains unknown whether it regulates emotion in a development-dependent manner. Here, by using mice with genetic deletion of GABAA(δ)R (knockout) and their wild-type littermates, we examined the role of GABAA(δ)R in regulating anxiety-like behavior, as measured with open field test (OFT) and elevated plus maze during the transition from puberty to adulthood.

Chronic Stress Causes Projection-Specific Adaptation of Amygdala Neurons via Small-Conductance Calcium-Activated Potassium Channel Downregulation.

Background: The role of the amygdala in mediating stress coping has been long appreciated. However, basolateral amygdala (BLA) projection neurons (PNs) are organized into discrete output circuits, and it remains unclear whether stress differentially impacts these circuits.

Methods: Mice were exposed to acute restraint stress or chronic restraint stress (CRS), and c-fos expression was measured as a proxy for neuronal activation in Retrobead retrogradely labeled dorsomedial prefrontal cortex-targeting PNs (BLA→dmPFC) and non-dmPFC-targeting PNs (BLA↛dmPFC).

Harmine enhances GABAergic transmission onto basoamygdala projection neurons in mice.

Emerging evidence indicates that loss of inhibitory tone in amygdala with its subsequent overactivation contributes to the development of multiple mental disorders such as anxiety disorders and post-traumatic stress disorder (PTSD). Harmine is a member of natural β-carboline alkaloids which can readily cross the blood brain barrier and displays significant antidepressant and anxiolytic effects in rodents. However, the underlying neurobiological mechanisms are largely unknown.

Chronic microaspiration of bile acids induces lung fibrosis through multiple mechanisms in rats.

Gastroesophageal reflux (GER) and microaspiration of duodenogastric refluxate have been recognized as a risk factor for pulmonary fibrosis. Recent evidence suggests that bile acid microaspiration may contribute to the development of lung fibrosis. However, the molecular evidence is scarce and the underlying mechanisms remain to be elucidated.

Overexpression of farnesoid X receptor in small airways contributes to epithelial to mesenchymal transition and COX-2 expression in chronic obstructive pulmonary disease.

Background: Epithelial-mesenchymal transition (EMT) and cyclooxygenase-2 (COX-2) contribute to airway remodelling and inflammation in chronic obstructive pulmonary disease (COPD). Recent data suggest that the farnesoid X receptor (FXR), a nuclear receptor traditionally considered as bile acid-activated receptor, is also expressed in non-classical bile acids target tissues with novel functions beyond regulating bile acid homeostasis. This study aimed to investigate the potential role of FXR in the development of COPD, as well as factors that affect FXR expression.

Bile acids induce activation of alveolar epithelial cells and lung fibroblasts through farnesoid X receptor-dependent and independent pathways.

Background And Objective: The roles of bile acid microaspiration and bile acid-activated farnesoid X receptor (FXR) in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remain unclear. We hypothesized that bile acids activate alveolar epithelial cells (AECs) and lung fibroblasts, which may be regulated by FXR activation.

Methods: Human AECs and normal or IPF-derived lung fibroblast cells were incubated with the three major bile acids: lithocholic acid (LCA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA).

Application of a stand-alone anchored spacer in noncontiguous anterior cervical arthrodesis with radiologic analysis of the intermediate segment.

The purpose of this study was to describe the clinical features of noncontiguous cervical degenerative disc disease (cDDD), investigate the efficacy and complications of a stand-alone anchored spacer (SAAS) for patients with noncontiguous cDDD, and present radiologic analysis of the intermediate segment (IS) after skip-level fusion. Nineteen consecutive patients with noncontiguous cDDD who underwent skip-level anterior cervical discectomy and fusion (ACDF) with SAAS from January 2010 to December 2012 were enrolled in this study. Clinical outcomes were assessed preoperatively and at 24 months postoperatively using the Japanese Orthopaedic Association score, Neck Disability Index, and Visual Analog Scale.

Immune Regulation of Interleukin-27 in Malignant Pleural Effusion.

Background: Interleukin (IL)-27 has been reported to have anti-proliferate and anti-angiogenic activities on cancer cells. However, the involvement of IL-27 in malignant pleural effusion (MPE) remains unknown. Thus, in this research, we compared the immune functions of IL-27, interferon (IFN)-γ, and IL-17 on lung cancer cells and revealed the regulatory mechanism of IL-27 in MPE.

IL-27 and IL-27-producing CD4+ T cells in human tuberculous pleural effusion.

The objective of the present study was to figure out whether human IL-27-producing CD4(+) T cells represent a distinct T cell subset in tuberculosis pleural effusion (TPE). Distribution, phenotypic features of IL-27-producing CD4(+) T cells in TPE were determined. The required transcription factors and signal transductions for IL-27-producing CD4(+) T cell differentiation were explored.