Increasing evidence suggests that depression may be associated with a lack of hippocampal neurogenesis. It is well established that neuronal nitric oxide synthase (nNOS)-derived NO exerts a negative control on the hippocampal neurogenesis. Using genetic and pharmacological methods, we investigated the roles of nNOS in depression induced by chronic mild stress (CMS) in mice. Hippocampal nNOS over-expression was first observed 4 days and remained elevated 21 and 56 days after exposure to CMS. The mice exposed to CMS exhibited behavioral changes typical of depression, and impaired neurogenesis in the hippocampus. The CMS-induced behavioral despair and hippocampal neurogenesis impairment were prevented and reversed in the null mutant mice lacking nNOS gene (nNOS)/)) and in the mice receiving nNOS inhibitor. Disrupting hippocampal neurogenesis blocked the antidepressant effect of nNOS inhibition. Moreover, nNOS)/) mice exhibited antidepressant-like properties. Our findings suggest that nNOS over-expression in the hippocampus is essential for chronic stress-induced depression and inhibiting nNOS signaling in brain may represent a novel approach for the treatment of depressive disorders.

Canine parvovirus disease is an acute infectious disease caused by canine parvovirus (CPV). Current commercial vaccines are mainly attenuated and inactivated; as such, problems concerning safety may occur. To resolve this problem, researchers developed virus-like particles (VLPs) as biological nanoparticles resembling natural virions and showing high bio-safety. This property allows the use of VLPs for vaccine development and mechanism studies of viral infections. Tissue-specific drug delivery also employs VLPs as biological nanomaterials. Therefore, VLPs derived from CPV have a great potential in medicine and diagnostics. In this study, small ubiquitin-like modifier (SUMO) fusion motif was utilized to express a whole, naturalVP2 protein of CPV in Escherichia coli. After the cleavage of the fusion motif, the CPV VP2 protein has self-assembled into VLPs. The VLPs had a size and shape that resembled the authentic virus capsid. However, the self-assembly efficiency of VLPs can be affected by different pH levels and ionic strengths. The mice vaccinated subcutaneously with CPV VLPs and CPV-specific immune responses were compared with those immunized with the natural virus. This result showed that VLPs can effectively induce anti-CPV specific antibody and lymphocyte proliferation as a whole virus. This result further suggested that the antigen epitope of CPV was correctly present on VLPs, thereby showing the potential application of a VLP-based CPV vaccine.

s Several lines of evidence suggest involvement of NMDA receptors (NMDARs) in the regulation of neurogenesis in adults and the formation of spatial memory. Functional properties of NMDARs are strongly influenced by the type of NR2 subunits incorporated. In adult forebrain regions such as the hippocampus and cortex, only NR2A and NR2B subunits are available to form the receptor complex with NR1 subunit. NR2B is predominant NR2 subunit in any of rat or human neural stem cells (NSCs). Thus, we suppose that NR2B‐containing NMDAR should be critical in regulating adult neurogenesis, and thereby playing a role in the formation of spatial memory. In the cultured NSCs derived from the embryonic brain of rats, NR2B subunit‐specific NMDAR antagonist Ro25‐6981 increased cell proliferation, whereas MK‐801, non‐selective open‐channel blocker of NMDARs, inhibited cell proliferation. Blockade of NR2B‐containing NMDAR stimulated neurogenesis in the adult hippocampus and facilitated the formation of spatial memory. The enhanced spatial memory dropped back to base level when the NR2B antagonist‐induced neurogenesis was neutralized by 3′‐azido‐deoxythymidine, a telomerase inhibitor. In addition, blockade of NR2B inhibited neuronal nitric oxide synthase (nNOS) enzymatic activity. In null mutant mice lacking nNOS gene (nNOS−/−), the effects of NR2B antagonist on neurogenesis disappeared. Moreover, nitric oxide donor DETA/NONOate attenuated and nNOS inhibitor 7‐nitroindazole enhanced the effect of Ro 25‐6981 on NSCs proliferation. Our findings suggest that NR2B‐containing NMDAR subtypes negatively regulate neurogenesis in the adult hippocampus by activating nNOS activity and thereby hinder the formation of spatial memory.