Restorative effect of NitroSynapsin on synaptic plasticity in an animal model of depression.

In the search for new options for the pharmacological treatment of major depressive disorder, compounds with a rapid onset of action and high efficacy but lacking a psychotomimetic effect are of particular interest. In the present study, we evaluated the antidepressant potential of NitroSynapsin (NS) at behavioural, structural, and functional levels. NS is a memantine derivative and a dual allosteric N-methyl-d-aspartate receptors (NMDAR) antagonist using targeted delivery by the aminoadamantane of a warhead nitro group to inhibitory redox sites on the NMDAR. In a chronic restraint stress (CRS) mouse model of depression, five doses of NS administered on three consecutive days evoked antidepressant-like activity in the chronically stressed male C57BL/6J mice, reversing CRS-induced behavioural disturbances in sucrose preference and tail suspension tests. CRS-induced changes in morphology and density of dendritic spines in cerebrocortical neurons in the medial prefrontal cortex (mPFC) were also reversed by NS. Moreover, CRS-induced reduction in long-term potentiation (LTP) in the mPFC was found to be prevented by NS based on the electrophysiological recordings. Our study showed that NS restores structural and functional synaptic plasticity and reduces depressive behaviour to the level found in naïve animals. These results preliminarily revealed an antidepressant-like potency of NS.

Oleanolic acid enhances neural stem cell migration, proliferation, and differentiation in vitro by inhibiting GSK3ß activity.

Oleanolic acid (OA), one of the bioactive ingredients in ginseng, has been reported to have neuroprotective activities. However, the effects and its mechanism on neural stem cell (NSC) induction are not entirely clear. In the present study, we investigated the effects of OA on promoting the migration, proliferation, and differentiation of neural stem cells (NSCs). Migration and proliferation were investigated by using neural-specific markers, neurosphere assay, and Cell Counting Kit-8, respectively. We found OA remarkably promoted neural migration and proliferation of NSCs in a time- and dose-dependent manner. Differentiation was analyzed by western blotting and immunofluorescence staining, which found MAP2 expression was remarkably increased, whereas Nestin was dramatically decreased. In addition, OA increased phosphorylation of GSK3ß at Ser9 and expression of active forms of ß-catenin. Furthermore, NSCs with constitutively active GSK3ß (S9A) significantly suppressed the OA-induced proliferation and neural differentiation. These results showed that OA could stimulate NSC proliferation and neural differentiation in vitro via suppressing the activity of GSK3ß. Our findings may have significant implications for the treatment of neurodegenerative diseases.

Exploring tuberculosis by types of housing development.

Tuberculosis (TB) is known as a disease of poverty. It has also been related to poor living environment. This study examines the relationship between TB outcome and housing characteristics which is reflective of the socio-economic standing. We sought to investigate the association from two novel angles: (1) TB outcome against floor level of residence, and (2) TB outcome against types of housing development. A total of 1787 culture-positive TB cases were collected by the Centralized Mycobacterium Laboratory from 2007 to 2009. Most of the cases fell in the catchment area of the Kowloon West Cluster, a densely populated urban area in Hong Kong. The distribution of culture-positive TB cases by floor levels of residence and types of housing was examined by descriptive and non-parametric statistical analyses. The effects of vertical distance of residence from the street level on TB outcome by different types of housing development were further explored by regression methods. Our study confirmed more TB cases among tenants on the lower floors and observed a decreasing trend towards higher floors. It also revealed that significantly more TB cases were residing in public as opposed to private or other types of housing (Chi-square = 151.14, p < 0.0001). Regression analysis by different housing types showed significantly different rates of change between floor number and TB cases (p < 0.0001). Our findings offer evidence on the inverse associations between floor levels of residence and TB occurrences and showed that the patterns were dependent on housing types. We demonstrated how housing characteristics could be useful input in an ecological study of the TB disease. These results have significant design and health implications for Asian cities that are getting denser and growing taller.

Risk of tuberculosis in high-rise and high density dwellings: an exploratory spatial analysis.

Studies have shown that socioeconomic and environmental factors have direct/indirect influences on TB. This research focuses on TB prevalence of Hong Kong in relation to its compact urban development comprising of high-rise and high-density residential dwellings caused by rapid population growth and limited land resources. It has been postulated that occupants living on higher levels of a building would benefit from better ventilation and direct sunlight and thus less likely to contract infectious respiratory diseases. On the contrary, those on lower floors amid the dense clusters of high-rises are more susceptible to TB infection because of poorer air quality from street-level pollution and lesser exposure to direct sunlight. However, there have not been published studies to support these claims. As TB continues to threaten public health in Hong Kong, this study seeks to understand the effects of housing development on TB occurrences in an urban setting.