138 research outputs found
Characterization of spatio-temporal epidural event-related potentials for mouse models of psychiatric disorders.
Distinctive features in sensory event-related potentials (ERPs) are endophenotypic biomarkers of psychiatric disorders, widely studied using electroencephalographic (EEG) methods in humans and model animals. Despite the popularity and unique significance of the mouse as a model species in basic research, existing EEG methods applicable to mice are far less powerful than those available for humans and large animals. We developed a new method for multi-channel epidural ERP characterization in behaving mice with high precision, reliability and convenience and report an application to time-domain ERP feature characterization of the Sp4 hypomorphic mouse model for schizophrenia. Compared to previous methods, our spatio-temporal ERP measurement robustly improved the resolving power of key signatures characteristic of the disease model. The high performance and low cost of this technique makes it suitable for high-throughput behavioral and pharmacological studies
Restoration of Sp4 in Forebrain GABAergic Neurons Rescues Hypersensitivity to Ketamine in Sp4 Hypomorphic Mice.
BackgroundKetamine produces schizophrenia-like behavioral phenotypes in healthy people. Prolonged ketamine effects and exacerbation of symptoms after the administration of ketamine have been observed in patients with schizophrenia. More recently, ketamine has been used as a potent antidepressant to treat patients with major depression. The genes and neurons that regulate behavioral responses to ketamine, however, remain poorly understood. Sp4 is a transcription factor for which gene expression is restricted to neuronal cells in the brain. Our previous studies demonstrated that Sp4 hypomorphic mice display several behavioral phenotypes relevant to psychiatric disorders, consistent with human SP4 gene associations with schizophrenia, bipolar disorder, and major depression. Among those behavioral phenotypes, hypersensitivity to ketamine-induced hyperlocomotion has been observed in Sp4 hypomorphic mice.MethodsIn the present study, we used the Cre-LoxP system to restore Sp4 gene expression, specifically in either forebrain excitatory or GABAergic inhibitory neurons in Sp4 hypomorphic mice. Mouse behavioral phenotypes related to psychiatric disorders were examined in these distinct rescue mice.ResultsRestoration of Sp4 in forebrain excitatory neurons did not rescue deficient sensorimotor gating nor ketamine-induced hyperlocomotion. Restoration of Sp4 in forebrain GABAergic neurons, however, rescued ketamine-induced hyperlocomotion, but did not rescue deficient sensorimotor gating.ConclusionsOur studies suggest that the Sp4 gene in forebrain GABAergic neurons regulates ketamine-induced hyperlocomotion
Recommended from our members
The influence of local officials' promotion incentives on carbon emission in Yangtze River Delta, China
China's carbon emissions is heavily influenced by economic growth, which can be largely related to the local officials' promotion incentives. The current study was conducted to test the hypothesis that the influence of local officials' individual characteristics on carbon emissions was driven by the promotion incentives. Yangtze River Delta where carbon emissions accounted for around 13.95% of China's total emissions was selected as the research area. The multiple linear regression model was applied to determine the relationship between local officials' characteristics and total carbon emissions and carbon emissions from different sectors. The results indicated that local officials' promotion source, tenure and age significantly influenced the total carbon emission. Despite insignificance influence of officials' academic level on carbon emissions, the professional background in economics and management had a significant influence on carbon reduction. Our results indicated the importance of local officials' promotion incentives for carbon emission in China. Therefore, low carbon development should be included as an important part of official promotion system
System-Wide Immunohistochemical Analysis of Protein Co-Localization
Background: The analysis of co-localized protein expression in a tissue section is often conducted with immunofluorescence histochemical staining which is typically visualized in localized regions. On the other hand, chromogenic immunohistochemical staining, in general, is not suitable for the detection of protein co-localization. Here, we developed a new protocol, based on chromogenic immunohistochemical stain, for system-wide detection of protein co-localization and differential expression. Methodology/Principal Findings: In combination with a removable chromogenic stain, an efficient antibody stripping method was developed to enable sequential immunostaining with different primary antibodies regardless of antibody’s host species. Sections were scanned after each staining, and the images were superimposed together for the detection of protein co-localization and differential expression. As a proof of principle, differential expression and co-localization of glutamic acid decarboxylase67 (GAD67) and parvalbumin proteins was examined in mouse cortex. Conclusions/Significance: All parvalbumin-containing neurons express GAD67 protein, and GAD67-positive neurons that do not express parvalbumin were readily visualized from thousands of other neurons across mouse cortex. The method provided a global view of protein co-localization as well as differential expression across an entire tissue section. Repeate
Ethnobotany of dye plants in Dong communities of China
BACKGROUND: Dyes derived from plants have an extensive history of use for coloring food and clothing in Dong communities and other indigenous areas in the uplands of China. In addition to use as coloring agents, Dong communities have historically utilized dye plants for their value for enhancing the nutritive, medicinal and preservative properties of foods. However, the persistence of plant-derived dyes and associated cultural practices and traditional knowledge is threatened with rapid socio-economic change in China. Research is needed to document the ethnobotany of dye plants in indigenous communities towards their conservation and potential commercialization as a sustainable means of supporting local development initiatives. METHODS: Semi-structured surveys on plants used for coloring agents and associated traditional knowledge were conducted in fifteen Dong villages of Tongdao County in Hunan Province of South Central China during 2011–2012. Transect walks were carried out with key informants identified from semi-structured surveys to collect samples and voucher specimens for each documented plant species for taxonomic identification. RESULTS: Dong households at the study sites utilize the flowers, bark, stems, tubers and roots of 13 plant species from 9 families as dyes to color their customary clothing and food. Out of the documented plants, a total of 7 are used for coloring food, 3 for coloring clothing and 3 for both food and clothing. Documented plants consist of 3 species that yield black pigments, 3 for brownish red/russet pigments, 3 for red pigments, 2 for dark blue pigments and 2 for yellow pigments. In addition to dyes, the plants have multiple uses including medicinal, ornamental, sacrificial, edible, and for timber. CONCLUSIONS: The use of dyes derived from plants persists at the study sites for their important role in expressing Dong cultural identity through customary clothing and food. Further research is needed to evaluate the safety of dye plants, their efficacy in enhancing food items and their commercial potential. Conservation policies and management plans are called for to preserve these ethnobotanical resources in a sustainable manner that supports local livelihoods while maintaining cultural practices
Core-shell NaHoF4@TiO2 NPs: A labelling method to trace engineered nanomaterials of ubiquitous elements in the environment
Understanding the fate and behavior of nanoparticles (NPs) in the natural environment is important to assess
their potential risk. Single particle inductively coupled plasma mass spectrometry (spICP-MS) allows for the detection of NPs at
extremely low concentrations, but the high natural background of the constituents of many of the most widely utilized nanoscale
materials makes accurate quantification of engineered particles challenging. Chemical doping, with a less naturally abundant
element, is one approach to address this; however, certain materials with high natural abundance, such as TiO2 NPs, are
notoriously difficult to label and differentiate from natural NPs. Using the low abundance rare earth element Ho as a marker,
Ho-bearing core -TiO2 shell (NaHoF4@TiO2) NPs were designed to enable the quantification of engineered TiO2 NPs in real
environmental samples. The NaHoF4@TiO2 NPs were synthesized on a large scale (gram), at relatively low temperatures, using
a sacrificial Al(OH)3 template that confines the hydrolysis of TiF4 within the space surrounding the NaHoF4 NPs. The resulting
NPs consist of a 60 nm NaHoF4 core and a 5 nm anatase TiO2 shell, as determined by TEM, STEM-EDX mapping, and spICPMS. The NPs exhibit excellent detectability by spICP-MS at extremely low concentrations (down to 1 × 10−3 ng/L) even in
complex natural environments with high Ti background
Heritable Differences in Catecholamine Signaling Modulate Susceptibility to Trauma and Response to Methylphenidate Treatment: Relevance for PTSD
Alterations in cortical catecholamine signaling pathways can modulate acute and enduring responses to trauma. Heritable variation in catecholamine signaling is produced by a common functional polymorphism in the catechol-O-methyltransferase (COMT), with Val carriers exhibiting greater degradation of catecholamines than Met carriers. Furthermore, it has recently been suggested that drugs enhancing cortical catecholamine signaling may be a new therapeutic approach for posttraumatic stress disorder (PTSD) patients. We hypothesized that heritable differences in catecholamine signaling regulate the behavioral response to trauma, and that methylphenidate (MPD), a drug that preferentially blocks catecholamine reuptake in the prefrontal cortex (PFC), exerts COMT-dependent effects on trauma-induced behaviors. We first examined the contribution of the functional mutation COMTval158met to modulate enduring behavioral responses to predator stress in a unique “humanized” COMTval158met mouse line. Animals were exposed to a predator (cat) for 10 min and enduring avoidance behaviors were examined in the open field, light-dark box, and “trauma-reminder” tests 1–2 weeks later. Second, we examined the efficacy of chronic methylphenidate to reverse predator stress effects and if these effects were modulated by COMTval158met genotype. Mice were exposed to predator stress and began treatment with either saline or methylphenidate (3 mg/kg/day) 1 week after stress until the end of the testing [avoidance behaviors, working memory, and social preference (SP)]. In males, predator stress and COMTval158met had an additive effect on enduring anxiety-like behavior, with Val stressed mice showing the strongest avoidance behavior after stress compared to Met carriers. No effect of COMT genotype was observed in females. Therefore methylphenidate effects were investigated only in males. Chronic methylphenidate treatment reversed the stress-induced avoidance behavior and increased social investigation independently of genotype. Methylphenidate effects on working memory, however, were genotype-dependent, decreasing working memory in non-stressed Met carriers, and improving stress-induced working memory deficit in Val carriers. These results suggest that heritable variance in catecholamine signaling modulates the avoidance response to an acute trauma. This work supports recent human findings that methylphenidate might be a therapeutic alternative for PTSD patients and suggests that methylphenidate effects on anxiety (generalized avoidance, social withdrawal) vs. cognitive (working memory) symptoms may be modulated through COMT-independent and dependent mechanisms, respectively
Spatio-temporal variations of health costs caused by chemical fertilizer utilization in China from 1990 to 2012
The health impacts caused by chemical fertilizer utilization have challenged long-term sustainable development in many countries, particularly developing countries. Based on the emergy analysis method, we estimated the temporal and spatial variations of the health costs, through atmospheric, water, and soil pathways, of chemical fertilizer utilization in China during the period from 1990 to 2012. The results showed an obvious increasing trend of health costs from 1.8 billion Yuan in 1990 to 23.0 billion Yuan in 2012, while the ratio of health costs to agriculture output value declined slowly and became stable in recent years. Regional differences were remarkable and were significantly correlated to the levels of economic development (r = 0.843 and p < 0.001) and crop-sown area in the region (r = 0.588 and p < 0.001). Economically developed regions, especially the eastern coastal provinces, had much higher costs than the western regions. Meanwhile, fertilizer consumption shifted from the eastern to the northwest region, which was the same as the health costs. This study provides a reference to estimate the health costs of fertilizer utilization, and the results highlight the importance of sustainable development in China
Core-Shell NaHoF<sub>4</sub>@TiO<sub>2</sub> NPs:a labeling method to trace engineered nanomaterials of ubiquitous elements in the environment
Understanding
the fate and behavior of nanoparticles (NPs) in the
natural environment is important to assess their potential risk. Single
particle inductively coupled plasma mass spectrometry (spICP-MS) allows
for the detection of NPs at extremely low concentrations, but the
high natural background of the constituents of many of the most widely
utilized nanoscale materials makes accurate quantification of engineered
particles challenging. Chemical doping, with a less naturally abundant
element, is one approach to address this; however, certain materials
with high natural abundance, such as TiO<sub>2</sub> NPs, are notoriously
difficult to label and differentiate from natural NPs. Using the low
abundance rare earth element Ho as a marker, Ho-bearing core -TiO<sub>2</sub> shell (NaHoF<sub>4</sub>@TiO<sub>2</sub>) NPs were designed
to enable the quantification of engineered TiO<sub>2</sub> NPs in
real environmental samples. The NaHoF<sub>4</sub>@TiO<sub>2</sub> NPs
were synthesized on a large scale (gram), at relatively low temperatures,
using a sacrificial Al(OH)<sub>3</sub> template that confines the
hydrolysis of TiF<sub>4</sub> within the space surrounding the NaHoF<sub>4</sub> NPs. The resulting NPs consist of a 60 nm NaHoF<sub>4</sub> core and a 5 nm anatase TiO<sub>2</sub> shell, as determined by
TEM, STEM-EDX mapping, and spICP-MS. The NPs exhibit excellent detectability
by spICP-MS at extremely low concentrations (down to 1 × 10<sup>–3</sup> ng/L) even in complex natural environments with high
Ti background
Cyr61 is involved in neutrophil infiltration in joints by inducing IL-8 production by fibroblast-like synoviocytes in rheumatoid arthritis
- …