Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca²⁺ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.     

Methylated arsenic metabolites bind to PML protein but do not induce cellular differentiation and PML-RARα protein degradation

Arsenic trioxide (As₂O₃) is one of the most effective therapeutic agents used for patients with acute promyelocytic leukemia (APL). The probable explanation for As₂O₃-induced cell differentiation is the direct targeting of PML-RARα oncoprotein by As₂O₃, which results in initiation of PML-RARa degradation. However, after injection, As₂O₃ is rapidly methylated in body to different intermediate metabolites such as trivalent monomethylarsonous acid (MMA^III) and dimethylarsinous acid (DMA^III), therefore, it remains unknown that which arsenic specie is actually responsible for the therapeutic effects against APL. Here we have shown the role of As₂O₃ (as iAs^III) and its intermediate metabolites (i.e., MMA^III/DMA^III) in NB4 cells. Inorganic iAs^III predominantly showed induction of cell differentiation, while MMA^III and DMA^III specifically showed to induce mitochondria and endoplasmic reticulum-mediated apoptosis, respectively. On the other hand, in contrast to iAs^III, MMA^III showed stronger binding affinity for ring domain of PML recombinant protein, however, could not induce PML protein SUMOylation and ubiquitin/proteasome degradation. In summary, our results suggest that the binding of arsenicals to the ring domain of PML proteins is not associated with the degradation of PML-RARa fusion protein. Moreover, methylated arsenicals can efficiently lead to cellular apoptosis, however, they are incapable of inducing NB4 cell differentiation.     

Associations of self-esteem,dysfunctional beliefs and coping style with depression in patients with schizophrenia: A preliminary survey

Psychological models of depression in schizophrenia have proposed that cognitive structures (e.g., self-esteem, dysfunctional beliefs) may have a role in the development and maintenance of depression. However, it has not been clear what the characteristics of these cognitive structures were in people with schizophrenia and whether they have an independent association with depression, especially in those from a Chinese cultural background. The present investigation examined 133 people with schizophrenia and 50 healthy controls and indicated that compared to the controls people with schizophrenia showed lower self-esteem, higher levels of dysfunctional beliefs and negative coping styles. Multiple linear regression analysis revealed that only low frustration tolerance, problem solving and self-blame were found to be the independent correlates of depression in schizophrenia. Results are discussed with the view of clinical implications of cognitive formulation and therapy for schizophrenia in China.     

应用辣根过氧化物酶逆行示踪技术观察左右侧脊神经节间纤维联系

目的:观察大鼠左右侧脊神经节之间的纤维联系,以寻找两侧脊神经节 (背根节)的神经元交互支配这一电生理学现象的形态学基础。方法:实验于2004-11／2005-03在首都医科大学人体解剖学系解剖学实验室进行,取Wistar大鼠48只,根据注射示踪剂的不同随机分为3 组:游离辣根过氧化物酶(300-500g/L)组,麦芽凝集素结合辣根过氧化物酶(10-50 g／L)组和霍乱毒素B单位结合辣根过氧化物酶(3g／L) 组,按注射部位不同又分为左侧脊髓(L3或L4)、左侧脊神经节(L3或L4)、左侧坐骨神经和左侧股神经4小组,每小组4只,注射量均为3μL。注射示踪剂后两三天麻醉状态下处死取材,钨酸钠法显色。观察各组动物左右侧脊神经节、脊髓组织切片阳性标记的细胞及纤维。结果:48只全部进入结果分析。无论注射哪种标记物,一侧神经、神经节注射辣根过氧化物酶仅在单侧前角有标记细胞,背外侧束、后角、中央管后灰质处有标记的纤维,个别对侧可见标记的纤维,偶见一两个标记细胞。脊髓一侧注射的除同侧有标记细胞外,对侧(脊髓、神经节)也有少量标记细胞。结论:一侧背根节细胞的中枢突可达到两侧后角,不能直接定论是否存在或不存在直接联系,还需要进行深入的电镜和神经递质研究。     

巴布剂基质配比的研究

目的 优选巴布剂基质配比.方法 采用正交试验设计法选择基质配比.以初黏力,剥离强度和内聚力的综合黏性得分为基质考察指标,对结果进行直观分析和方差分析.结果 优选基质配比为聚乙二醇:阿拉伯胶:卡波姆:聚丙烯酸钠=2∶1∶3∶2.结论 按优选最佳条件制备的巴布剂具有良好的延展性,外观平整光滑,且能满足黏弹性要求.