mGluR5 in hippocampal CA1 pyramidal neurons mediates stress-induced anxiety-like behavior.

Pharmacological manipulation of mGluR5 has showed that mGluR5 is implicated in the pathophysiology of anxiety and mGluR5 has been proposed as a potential drug target for anxiety disorders. Nevertheless, the mechanism underlying the mGluR5 involvement in stress-induced anxiety-like behavior remains largely unknown. Here, we found that chronic restraint stress induced anxiety-like behavior and decreased the expression of mGluR5 in hippocampal CA1. Specific knockdown of mGluR5 in hippocampal CA1 pyramidal neurons produced anxiety-like behavior. Furthermore, both chronic restraint stress and mGluR5 knockdown impaired inhibitory synaptic inputs in hippocampal CA1 pyramidal neurons. Notably, positive allosteric modulator of mGluR5 rescued stress-induced anxiety-like behavior and restored the inhibitory synaptic inputs. These findings point to an essential role for mGluR5 in hippocampal CA1 pyramidal neurons in mediating stress-induced anxiety-like behavior.

Cellular signaling pathways of T cells in giant cell arteritis.

Giant cell arteritis (GCA) is a commonly occurring large vacuities characterized by angiopathy of medium and large-sized vessels. GCA granulomatous formation plays an important role in the pathogenesis of GCA. Analysis of T cell lineages and signaling pathways in GCA have revealed the essential role of T cells in the pathology of GCA. T cells are the dominant population present in GCA lesions. CD4+ T cell subtypes that are present include Th1, Th2, Th9, Th17, follicular helper T (Tfh) cells, and regulatory T (Treg) cells. CD8 T cells can primarily differentiate into cytotoxic CD8+ T lymphocytes and Treg cells. The instrumental part of GCA is the interplay between dendritic cells, macrophages and endothelial cells, which can result in the vascular injury and the characteristics granulomatous infiltrates formation. During the inflammatory loop of GCA, several signaling pathways have been reported to play an essential role in recruiting, activating and differentiating T cells, including T-cell receptor (TCR) signaling, vascular endothelial growth factor (VEGF)-Jagged-Notch signaling and the Janus kinase and signal transducer and activator of transcription (STAT) pathway (JAK-STAT) pathway. In this review, we have focused on the role of T cells and their potential signaling mechanism (s) that are involved in the pathogenesis of GCA. A better understanding of the role of T cells mediated complicated orchestration during the homeostasis and the changes could possibly favor developments of novel treatment strategies against immunological disorders associated with GCA.

Regulation of plasma lipid homeostasis by hepatic lipoprotein lipase in adult mice.

LPL is a pivotal rate-limiting enzyme to catalyze the hydrolysis of TG in circulation, and plays a critical role in regulating lipid metabolism. However, little attention has been paid to LPL in the adult liver due to its relatively low expression. Here we show that endogenous hepatic LPL plays an important physiological role in plasma lipid homeostasis in adult mice. We generated a mouse model with the Lpl gene specifically ablated in hepatocytes with the Cre/LoxP approach, and found that specific deletion of hepatic Lpl resulted in a significant decrease in plasma LPL contents and activity. As a result, the postprandial TG clearance was markedly impaired, and plasma TG and cholesterol levels were significantly elevated. However, deficiency of hepatic Lpl did not change the liver TG and cholesterol contents or glucose homeostasis. Taken together, our study reveals that hepatic LPL is involved in the regulation of plasma LPL activity and lipid homeostasis.

[Alterations of peripheral blood T cell subsets in patients with sepsis and the clinical implications].

OBJECTIVE: To observe the dynamic changes of CD3+, CD4+, and CD8+ T lymphocytes in the peripheral blood of patients with sepsis and discuss the clinical significance. METHODS: Sixty-four patients admitted in the Emergency Center and Emergency Intensive Care Unit of the Second Hospital of Wenzhou Medical University between August, 2007 and July, 2009 were enrolled in this study. CD3+, CD4+, and CD8+ T lymphocytes in the peripheral blood were detected by flow cytometry on days 1, 7 and 14 after admission, and the results were compared between the patients with improvement of the condition and those without improvement, with 20 healthy subjects as the control group. RESULTS: On day 1 after admission, CD3+ and CD4+ T lymphocytes and CD4+/CD8+ T cell ratio were obviously lower in the 2 groups of patients with sepsis than in the control group (P<0.05), but no significant difference was found in CD8+ T lymphocytes. The sepsis patients with clinical improvement showed significant higher CD3+ and CD4+ T lymphocyte percentages and CD4+/CD8+ T cell ratio than those without improvement on day 1. In the patients with clinical improvement, CD3+ and CD4+T lymphocytes and CD4+/CD8+ T cell ratio increased gradually with time and till day 14, they were comparable with the control levels; in the patients without improvement, CD3+ and CD4+ T lymphocytes and CD4+/CD8+ T cell ratio showed no obvious alterations in the course of observation. CONCLUSION: Immune imbalance occurs in patients with sepsis represented by lowered CD3+ and CD4+T lymphocyte percentages and CD4+/CD8+ T cell ratio in relation to the severity of the condition. CD3+ and CD4+ T lymphocytes and CD4+/CD8+ T cell ratio can be used as the indicators for assessing the severity of sepsis.