Anti-LINGO-1 antibody treatment alleviates cognitive deficits and promotes maturation of oligodendrocytes in the hippocampus of APP/PS1 mice.

Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1), a negative regulator of oligodendrocyte differentiation and myelination, is associated with cognitive function, and its expression is highly upregulated in Alzheimer's disease (AD) patients. Anti-LINGO-1 antibody treatment can effectively antagonize the negative regulatory effect of LINGO-1. In this study, we aim to assess the effect of anti-LINGO-1 antibody treatment on cognition and hippocampal oligodendrocytes in an AD transgenic animal model. First, 10-month-old male amyloid-ß (Aß) protein precursor (APP)/presenilin 1 (PS1) mice were administered anti-LINGO-1 antibody for 8 weeks. Then, learning and memory abilities were assessed with the Morris water maze (MWM) and Y-maze tests, and Aß deposition and hippocampal oligodendrocytes were investigated by immunohistochemistry, immunofluorescence, and stereology. We found that anti-LINGO-1 antibody alleviated the deficits in spatial learning and memory abilities and working and reference memory abilities, decreased the density of LINGO-1 positive cells, decreased Aß deposition, significantly increased the number of mature oligodendrocytes and the density of myelin, reversed the abnormal increases in the number of oligodendrocyte lineage cells and the densities of oligodendrocytes precursor cells in APP/PS1 mice. Our results provide evidence that LINGO-1 might be involved in the process of oligodendrocyte dysmaturity in the hippocampus of AD mice, and that antagonizing LINGO-1 can alleviate cognitive deficits in APP/PS1 mice and decrease Aß deposition and promote oligodendrocyte differentiation and maturation in the hippocampus of these mice. Our findings suggest that changes in LINGO-1 and oligodendrocytes in the hippocampus play important roles in the pathogenesis of AD and that antagonizing LINGO-1 might be a potential therapeutic strategy for AD.

Anti-Lingo-1 antibody ameliorates spatial memory and synapse loss induced by chronic stress.

Chronic stress can induce cognitive impairment, and synapse number was significantly decreased in the hippocampus of rats suffering from chronic stress. Lingo-1 is a potent negative regulator of axonal outgrowth and synaptic plasticity. In the current study, the effects of anti-Lingo-1 antibody on the spatial learning and memory abilities and hippocampal synapses of stressed rats were investigated. After 4 weeks of stress exposure, the model group was randomly divided into a chronic stress group and an anti-Lingo-1 group. Then, the anti-Lingo-1 group rats were treated with anti-Lingo-1 antibody (8 mg/kg) for 3 weeks. The effects of anti-Lingo-1 antibody on the spatial learning and memory abilities were investigated with the Morris water maze test. Immunohistological staining and an unbiased stereological method were used to estimate the total number of dendritic spine synapses in the hippocampus. At the behavioral level, after 3 weeks of treatment, the anti-Lingo-1 group rats displayed significantly more platform location crossings in the Morris water maze test than the chronic stress group rats. Anti-Lingo-1 significantly prevented the declines in dendritic spine synapses and postsynaptic density protein-95 (PSD-95) expression in the dentate gyrus and the CA1 and CA3 regions of the hippocampus. The present results indicated that anti-Lingo-1 antibody may be a safe and effective drug for alleviating memory impairment in rats after chronic stress and protecting synapses in the hippocampus of stressed rats.

[Forest lighting fire forecasting for Daxing'anling Mountains based on MAXENT model].

Daxing'anling Mountains is one of the areas with the highest occurrence of forest lighting fire in Heilongjiang Province, and developing a lightning fire forecast model to accurately predict the forest fires in this area is of importance. Based on the data of forest lightning fires and environment variables, the MAXENT model was used to predict the lightning fire in Daxing' anling region. Firstly, we studied the collinear diagnostic of each environment variable, evaluated the importance of the environmental variables using training gain and the Jackknife method, and then evaluated the prediction accuracy of the MAXENT model using the max Kappa value and the AUC value. The results showed that the variance inflation factor (VIF) values of lightning energy and neutralized charge were 5.012 and 6.230, respectively. They were collinear with the other variables, so the model could not be used for training. Daily rainfall, the number of cloud-to-ground lightning, and current intensity of cloud-to-ground lightning were the three most important factors affecting the lightning fires in the forest, while the daily average wind speed and the slope was of less importance. With the increase of the proportion of test data, the max Kappa and AUC values were increased. The max Kappa values were above 0.75 and the average value was 0.772, while all of the AUC values were above 0.5 and the average value was 0. 859. With a moderate level of prediction accuracy being achieved, the MAXENT model could be used to predict forest lightning fire in Daxing'anling Mountains.

[Genetic relationships among Fructus Aurantii cultivars revealed by ISSR].

OBJECTIVE: A total of 27 samples belonging to 5 cultivars of Fructus Aurantii (Citrus aurantium), i. e. cv. Xiucheng, cv. Xiangcheng, cv. Lecheng, cv. Jizicheng, and cv. Youzicheng, collected at Changfu and Huanggang, Zhangshu City, Jiangxi Province, were assayed to reveal the genetic relationship among the cultivars and the accordance between morphological and molecular markers. METHOD: Cultivar identification was based on morphology and cultivar relationship was based on Inter-simple sequence repeats (ISSR). RESULT: Twenty out of 40 ISSR primers screened generated 392 loci across all 27 samples with 315 informative loci. The UPGMA dendrogram showed that samples within cv. Xiucheng and cv. Xiangcheng from Changfu were closely related. However, samples of cv. Lecheng, cv. Jizicheng and cv. Youzicheng from Huanggang, or cv. Xiucheng and cv. Xiangcheng from both Changfu and Huanggang did not exhibited close relationships within each cultivars. CONCLUSION: Based on morphology the same cultivar grown in different plantations, or even within a single plantation sometimes do not show close genetic relationship, indicating diverse origin of the cultivars. Synonyms or homonyms are believed to common phenomenon in Fructus Aurantii production. To solve the problem ISSR markers can serve a kind of molecular markers which are preferable to partition genetic variations within and between cultivars and to establish genetic relationships among them.

[The value of reticulated platelet counts in diagnosing thrombocytopenic disorders].

OBJECTIVE: To evaluate the significance of reticulated platelets (RPs) in the diagnosis of thrombocytopenic disorders and the relationship between RPs and the proliferative degree of megakaryocyte (MK) in bone marrow. METHODS: With thiazole orange as a fluorescent dye, RPs were measured by analyzing the RNA content in platelets with flow cytometry and the percent and absolute counts of RPs were calculated. RESULTS: (1) The percent and absolute counts of the RPs in a normal group were (8.4 +/- 2.5)% and (16.8 +/- 6.8) x 10(9)/L respectively. (2) As compared with the normal group, the patients with idiopathic thrombocytopenic purpura (ITP) and hypersplenism had a significantly high percent and low absolute counts of RPs (P < 0.01). In patients with aplastic anemia, both the percent and absolute counts of RPs were at low levels (P < 0.05 and P < 0.01, respectively). There was no difference of RP percentage between the patients with acute leukemia or myelodysplastic syndromes and normal controls, but the absolute counts of RPs in the former was significantly lower than that in the latter. There was no difference between the percent and absolute counts of RPs among ITP patients with different proliferative degree of MK in bone marrow. (3) In all the diseases mentioned above, it was shown that RP percentage returned to normal in the effective cases after treatment, but no such change was found in the ineffective cases. CONCLUSIONS: Reticulated platelet counts contribute to the aetiology determination of the thrombocytopenia. It is also a valuable diagnostic method and a monitoring marker. There is no relationship between reticulated platelet counts and the counts of MK proliferation in bone marrow.