Epigenetic alterations of the BDNF gene in combat-related post-traumatic stress disorder.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) plays a crucial role in modulating resilience and vulnerability to stress. The aim of this study was to investigate whether epigenetic regulation of the BDNF gene is a biomarker of post-traumatic stress disorder (PTSD) development among veterans exposed to combat in the Vietnam War. METHODS: Using the Clinician-Administered PTSD Scale, combat veterans were grouped into those with (n = 126) and without (n = 122) PTSD. DNA methylation levels at four CpG sites within the BDNF promoter I region were quantified in the peripheral blood using pyrosequencing. The effects of BDNF DNA methylation levels and clinical variables on the diagnosis of PTSD were tested using binary logistic regression analysis. RESULTS: Subjects with PTSD showed a higher DNA methylation of four CpG sites at the BDNF promoter compared with those without PTSD. High methylation levels at the BDNF promoter CpG site, high combat exposure, and alcohol problems were significantly associated with PTSD diagnosis. CONCLUSIONS: This study demonstrated an association between higher DNA methylation of the BDNF promoter and PTSD diagnosis in combat-exposed individuals. Our findings suggest that altered BDNF methylation may be a valuable biomarker of PTSD after trauma exposure.

A dominant antigenic region of the hantaan virus nucleocapsid protein is located within a amino-terminal short stretch of hydrophilic residues.

The nucleocapsid (N) protein of the Hantaan virus (HTNV) is a major viral antigen that induces a strong antibody response during the acute phase of infection. By immunoblot analyses of the recombinant N proteins using human sera of the hemorrhagic fever with renal syndrome (HFRS), we have confirmed previous finding by other investigators of the presence of a highly antigenic region near the amino terminus of the HTNV N protein. We have further located the antigenic region within a short stretch of hydrophilic sequences between the 26 and the 46th amino acid residues. The recombinant glutathione S-transferase fusion proteins containing this region was expressed as a soluble form in a large quantity in Escherichia coli, and purified by a single-step affinity chromatography. The recombinant antigen also showed a similar, but a weaker reactivity with human antisera to Seoul virus (SEOV), the virus most closely related to HTNV.

Strain differences in the expression of corticotropin-releasing hormone immunoreactivity in nerves that supply the spleen and thymus.

The existence of nerve fibers containing corticotropin-releasing hormone (CRH) immunoreactivity in primary and secondary lymphoid organs from three strains of young adult male rats was examined. Spleens and thymuses from Fischer 344 (F344), Sprague-Dawley (SD) and Lewis (LEW) rats were prepared for immunocytochemistry using antisera directed against CRH. In F344 and SD rats, we were unable to demonstrate CRH-immunoreactive nerves in either the thymus or the spleen. Despite the lack of CRH-containing nerves, CRH immunoreactivity was present in pleotropic cells in the septum, cortex and medulla of the thymus, and in the red and white pulp of spleens from F344 and SD rats. In contrast, CRH+ nerves were found in thymuses and spleens from LEW rats. CRH+ nerves coursed in the interlobular septa, capsule, cortex and medulla of the LEW rat thymus. Large CRH-immunoreactive nerve bundles were present in the hilar region of the LEW rat spleen, and individual CRH+ fibers coursed in the capsule, trabeculae, red pulp, venous sinuses and marginal zone of the white pulp of the spleen. These findings indicate strain differences in neurotransmitter-specific nerves that innervate the rat spleen and thymus under basal conditions.

Apoptosis is induced by hantaviruses in cultured cells.

Hantaviruses replicate in primary and cultured animal cells with little or no cytopathic effect. We report here that the cultured Vero E6 cells infected by the Hantaan or by the Prospect Hill viruses exhibited characteristic features of apoptosis, including condensation and segmentation of nuclei and internucleosomal cleavage of nuclear DNA. Apoptosis was not seen in the cells adsorbed by UV-inactivated virus, indicating that the viral replication is required for the induction of apoptosis. Furthermore, level of the proto-oncogenic Bcl-2 protein was significantly reduced, whereas its mRNA level remained unchanged in Hantaan virus-infected cells, suggesting possible involvement and posttranscriptional regulation of this antiapoptotic protein in the process.