Role of KA1 receptor in excitotoxic neurodegeneration in mouse hippocampus triggered by kainic acid- or tunicamycin-induced endoplasmic reticulum stress / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of up-regulation of KA1 subunit of the kainate receptor on endoplasmic reticulum stress (ERS)-induced excitotoxic neurodegeneration in mouse hippocampus.</p><p><b>METHODS</b>Seventy adult male KM mice were subjected to microinjections into the hippocampus of kainic acid (KA) or 500, 1000, or 2000 µg/ml tunicamycin (TM). At 1, 2, 3, 4, 5, 8, and 12 h after the injections, the mice were assessed for Bederson scores and sacrificed for FJB staining and immunofluorescence observation of the brain slices.</p><p><b>RESULTS</b>At 3, 4, 5, and 8 h after KA injection and at 4 and 5 h after of 2000 µg/ml TM injection, the mice showed severe central nervous system dysfunction, and FJB staining revealed increased cell death in the hippocampus, where up-regulated expressions of KA1 receptor and ERS marker P-eIF2α were found by immunofluorescence staining (P<0.05).</p><p><b>CONCLUSION</b>Microinjection of KA or TM into the hippocampus causes neuronal death and ERS with up-regulated expression of KA1. In this process of neuronal apoptosis, the membrane receptor KA1 receives the apoptosis signal and transfers it to the inside of the cells to cause cell endoplasmic reticulum dysfunction and ERS response, which ultimately leads to neuronal death.</p>

Correlation research between single nucleotide polymorphism of methylenetetrahydrofolate reductase and Alzheimer′s disease in South China Han people / 实用医学杂志

Objective To investigate the relationship between single nucleotide polymorphism (677C→T) of methylenetetrahydrofolate reductase and Alzheimer′s disease(AD) in south China Han people. Methods By applying polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), MTHFR 677C→T mutation was detected in 45 AD patients and 48 healthy controls. Results The frequency of MTHFR 677C→T mutation of patients showed no significant difference to that of healthy controls (P > 0.05). There is no statistic significance between AD group and controls in C, T gene frequency(P>0.05). But T gene frequency is higher in AD group than in control group. Conclusion MTHFR C 677T is not the pathogenic factor for AD, but could have some effects on AD.

Feasibility of continuous extracorporeal normothermic liver perfusion using autologous blood: a study in pigs / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the feasibility of sustaining the viable status of a liver graft in at least 96 h by extracorporeal perfusion using autologous blood.</p><p><b>METHODS</b>Eight extracorporeal porcine liver perfusions using autologous blood were performed, each for 96 h with hepatectomy, cold preservation, cannulation of vessels, and initiation of perfusion with normothermic oxygenated porcine blood. The graft viability was assessed by metabolic, synthetic, hemodynamic, and histologic parameters.</p><p><b>RESULTS</b>After 96 h of normothermic, extracorporeal perfusion using autologous blood, the isolated livers maintained normal physiological levels of pH and electrolytes with sustained hepatic protein synthesis (complement and factor V) throughout the perfusion. Hemodynamic parameters maintained normal physiological ranges. Histological inspection demonstrated good preservation of the liver with a good architectural integrity.</p><p><b>CONCLUSION</b>It is possible to sustain the viable status of a liver graft within 96 h by extracorporeal perfusion using autologous blood.</p>

Kainic acid-induced endoplasmic reticulum stress model / 中国组织工程研究

BACKGROUND:Previous studies have shown that kainic acid injected into hippocampus can significantly upregulate the expression of excitatory KA1 subunit of the kainate receptor in the hippocampus, and endoplasmic reticulum stress markers, phosphorylation of the alpha subunit of eukaryotic initiation factor 2, accompanied by celldeath. OBJECTIVE:To explore the mechanism of endoplasmic reticulum stress after kainic acid is injected into the hippocampus.METHODS:0.15 nmol kainic acid was injected into the hippocampal CA1 region of 32 adult male Kunming mice, the injection time was 60 seconds. At different time points (1, 2, 3, 4, 5, 6, 8 and 12 hours) after kainic acid was injected, the Bederson score analysis was performed, and then the brain was harvested after cerebral perfusion. FJB staining of brain sections and immunofluorescence double labeled observation were also performed. RESULTS AND CONCLUSION:(1) At 3, 4, 5, 6, 8 hours after kainic acid injection, Bederson score showed severe injury of central nervous system function, and FJB staining showed the increased of celldeath in the hippocampus (P0.05). (2) According to the results of FJB staining, the brain sections were selected at 3, 8 hours for immunohistochemistry. The expressionlevels of KA1 receptors and endoplasmic reticulum stress marker P-eIF2αwere up-regulated at the same time after kainic acid was injected into hippocampus. Two single-staining KA1 and P-eIF2αimmunofluorescence images were synthesized into one over-lapped double-stained image, and two images overlapped, indicating that the up-regulated expression of KA1 and endoplasmic reticulum stress occurred in the same nerve cells. Kainic acid first up-regulated the excitatory receptor KA1 expression, which may cause cellendoplasmic reticulum dysfunction and result in the endoplasmic reticulum stress response, further promoting neuronal celldeath.