No abstract

Interferon-γ (IFN-γ) is a pleiotropic cytokine that is critical for innate and adaptive immunity. Recent evidence suggests a connection between IFN-γ signaling and the sonic hedgehog (Shh) pathway in the developing brain with CNS-targeted expression of IFN-γ transgene in mice. To determine the relationship between these distinct pathways, we have found that IFN-γ induces a rapid Shh transcription in cultured primary granular neuron precursor (GNP) cells. The transcriptional induction of Shh by IFN-γ is resistant to protein synthesis inhibition. Chromatin immunoprecipitation (ChIP) analysis reveals a direct binding of signal transducer and activator of transcription (STAT) 1 to the Shh promoter. Functional analyses, including dual immunofluorescent labeling with 5-bromodeoxyuridine (BrdU) incorporation indicate that IFN-γ treatment leads to significant GNP proliferation. This mitogenic effect of IFN-γ is blocked by inhibition of Shh signaling. Therefore, Shh is an IFN-γ target gene and is responsible for IFN-γ-induced GNP proliferation. This previously unrecognized crosstalk between IFN-γ and Shh highlights a potential importance of this immune mediator in the pathogenesis of human developmental and psychiatric disorders.

Background: The circulating estrogen concentration elevated gradually along with time after ovariectomy in rats. To explore the source of the increased circulation estrogen, the extragonadal aromatization as well as the synthesis of androgen in the adrenal cortex of the ovariectomized rats was evaluated.

Electroacupuncture (EA) could improve the hyperactivity of the hypothalamus pituitary adrenal (HPA) axis induced by hepatectomy. However, its underlying mechanism still remains largely unclear. Here, we found that hypothalamic corticotrophin releasing hormone (CRH) modulates the function of the HPA axis, while hepatectomy induced an HPA axis disorder and EA application could regulate the hypothalamic CRH. We first demonstrated that microRNAs (miRNAs) target on CRH via bioinformatics analysis and screened them in the primary hypothalamic neurons. MicroR-142 (miR-142) and miR-376c were identified to inhibit CRH at the mRNA and protein levels, and a dual luciferase reporter assay confirmed their binding to the 3′-untranslated regions (3′-UTR) of CRH. Further analyses revealed a decrease in hypothalamic miR-142 expression in the hepatectomy rats and an increase in miR-142 and miR-376c after EA intervention. Importantly, the improvement effect of EA on the HPA axis regulatory function in hepatectomy rats was blocked by miR-142 antagomir. Our findings illustrated that EA could up-regulate hypothalamic miR-142 expression and decrease the CRH level to alleviate the hyperactivity of the HPA axis induced by hepatectomy.

No abstract