Histamine Excites Rat GABAergic Ventral Pallidum Neurons via Co-activation of H1 and H2 Receptors / 神经科学通报·英文版

The ventral pallidum (VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion. Although the VP receives afferent inputs from the central histaminergic system, little is known about the effect of histamine on the VP and the underlying receptor mechanism. Here, we showed that histamine, a hypothalamic-derived neuromodulator, directly depolarized and excited the GABAergic VP neurons which comprise a major cell type in the VP and are responsible for encoding cues of incentive salience and reward hedonics. Both postsynaptic histamine H1 and H2 receptors were found to be expressed in the GABAergic VP neurons and co-mediate the excitatory effect of histamine. These results suggested that the central histaminergic system may actively participate in VP-mediated motivational and emotional behaviors via direct modulation of the GABAergic VP neurons. Our findings also have implications for the role of histamine and the central histaminergic system in psychiatric disorders.

protective effects of sufentanil pretreatment on rat brains under the state of cardiopulmonary bypass

This study aimed to observe the protective effects of sufentanil pretreatment on rat cerebral injury during cardiopulmonary bypass [CPB] and to explore the underlying mechanism. Twenty-four male adult Sprague Dawley [SD] rats were divided into 4 groups. Then, the rat CPB model was established. A 14G trocar was inserted into the atrium dextrum. For rats in S1 and S5 groups, sufentanil [1 microgKg[-1] and 5 microgKg[-1]] were applied before CPB process. After the operation, rat brain samples were harvested for measurement of the water content of the brains, total calcium in brain tissue and the level of serum S100beta. Compared with the Sham group, the water content and the total calcium of the brain tissue, and the expression of S100beta in serum were significantly increased in the CPB group [P<0.05]. Compared with the CPB group, sufentanil treatment significantly reduced the water content of the brains, the total calcium and S100beta expression [P<0.05]. The blood pressure and heart rate were significantly decreased in groups CPB, S1, and S5 compared with Sham group during CPB. Compared with the Sham group, the levels of pH and blood lactate in other groups were decreased and increased, respectively, in the post-CPB period. During the CPB and post-CPB periods, the hematocrit levels were significantly down-regulated in groups CPB, S1, and S5 compared with Sham group. In conclusion, sufentanil pretreatment was effective in reducing the cerebral injury during CPB. Reduction in calcium overload may be a potential mechanism in such process

Locally administered lentivirus-mediated siRNA inhibits wear debris-induced inflammation / 中华外科杂志

<p><b>OBJECTIVE</b>To determine the safety and efficacy of local administration of lentivirus-mediated small interfering RNA (siRNA) targeting tumor necrosis factor-alpha (TNF-alpha) in murine air pouch model.</p><p><b>METHODS</b>From May 2007 to April 2008 a siRNA targeting TNF-alpha and a missense siRNA were designed, and recombine lentivirus which coexpressed the green fluorescent protein (GFP) as a marker gene was constructed. Air pouches were established and stimulated by Ti-6Al-4V particles. Pouches were divided into 3 groups randomly. Lentivirus-mediated siRNA targeting TNF-alpha (TNF-alpha group) or lentivirus-mediated missense siRNA (MS group), or virus-free saline (control group) were injected into pouches respectively. Pouch membrane, peripheral blood, heart, liver, spleen, kidney, lung and brain were harvested at 28 d after transfection, and assayed for markers of inflammation using histological, molecular, immunological techniques and Xenogen in vivo imaging system (IVIS) 50 vivo bioluminescent assay system.</p><p><b>RESULTS</b>Xenogen IVIS 50 vivo image revealed strong expression of GFP localized in pouch areas and no expression in other parts of mice both in TNF-alpha group and MS group at 4 weeks after transfection, while no expression of GFP was found in control group. By RT-PCR and ELISA, the mRNA and protein levels of TNF-alpha in TNF-alpha group decreased by 81.6% and 82.6% respectively compared to control group (P < 0.01), and decreased by 78.9% and 84.0% respectively compared to MS group (P < 0.01), whereas TNF-alpha level in peripheral blood, heart, liver, spleen, kidney, lung and brain remained invariant (P > 0.05). Less inflammatory responses (thinner pouch membrane and decreased cellular infiltration) were observed in TNF-alpha group.</p><p><b>CONCLUSION</b>Efficient local delivery of lentivirus-mediated siRNA targeting TNF-alpha into modified murine air pouch can inhibit debris-induced inflammation effectively, with no systemic adverse effects.</p>

Human osteoblasts response to different magnitudes of mechanical stimulation in vitro / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of different magnitudes of tensile strain on human osteoblasts differentiation.</p><p><b>METHODS</b>According to the strain amplification mechanism at cellular level and a data calculated by finite element analysis, the cellular level strain of 0.8%, 1.6%, 2.4% and 3.2% was respectively applied to human osteoblasts for 48 h at a frequency of 1 Hz. Alkaline phosphatase activity and the expression of osteoblast-related genes were detected by Semi-Quantitative RT-PCR and densitometric analysis.</p><p><b>RESULTS</b>Alkaline phosphatase activity significantly increased at 0.8% and 1.6%. The level of osteocalcin mRNA increased at 2.4% and 3.2%. Cbfa1/Runx2 gene expression only increased at 3.2%. Comparing to static control, mRNA level of type I collagen increased at every magnitude. The mRNA level decreased at 0.8% and increased at 3.2% when compared to the group with 1.6% elongation.</p><p><b>CONCLUSIONS</b>Higher magnitudes of strain enhance expression of osteocalcin, type I collagen gene and Cbfa1/Runx2 in human osteoblasts, but lost the ability to increase ALP activity which is remained by lower magnitudes of strain. Type I collagen gene expression increases in a strain magnitude dependent manner.</p>