ABSTRACT
Objective To explore the effects of beta-amyloid precursor protein (APP17) peptide on the changes in the expressions of phosphoinositide 3-kinase(PI3K), protein kinase B(PKB) and phosphorylation of cAMP response element binding protein (p-CREB) in the neurons of hippocampal gyms in rats after cardiopulmonary resuscitation. Method Twenty-one Wistar rats were randomly divided into three groups, namely the sham-operated control group, the resuscitation group and resuscitation with APP17 peptide-treated group. The rat model of asphyxial cardiac arrest was made by clamping the endotracheal tube and the standard external cardiopulmonary resuscitation ( CPR) was performed until the restoration of spontaneous circulation ( ROSC) observed.ROSC was defined by the appearance of normal QRS waves of electrocardiogram and mean artery pressure ( MAP)≥60 mmHg for more than 10 minutes. Rats of resuscitation group and control group received intravenous 0.9%NaCl, and the rats of the APP17 peptide group were treated with APP17 peptide(10μg·300 g~(-1), i. v.) after ROSC. Rats were sacrificed by decapitation after reperfusion 2 hours and then the cerebral hippocampal gyrus was immediately separated to detect PI3K, PKB and p-CREB by immunohistochemistry ( IHC) and Western-blot analysis. Statistical comparisons were made by one-way analysis of variance (ANOVA) . Results IHC showed that there was no significant difference in PDK positive cells between resuscitation group and control group (2.75 ±1.80 vs. 2.53 ± 1.53, P > 0.05) . The PDK obviously more increased in the APP17 peptide group than in resuscitation group(5.85 ± 2.83 vs. 2.75 ± 1.80, P < 0.01) .The counts of PKB and p-CREB positive cells were obviously lower in resuscitation group than those in control group (2.45 ± 1.36 vs. 5.22 ± 2.50, P < 0.05);(2.41 ± 1.11 vs. 8.31 ±3.02, P < 0.01 ). The PKB and p-CREB positive cells were significantly higher in the APP17 peptide group than in resuscitation group (9.66±4.32 vs. 2.45 ±1.36, P < 0.01);(14.18 ± 3.96 vs.2.41 ± 1.11, P <0.01). The PKB and p-CREB protein levels in resuscitation group were lower than those in the control group. Conclusions The expressions of PKB and p-CREB in neurons of hippocampus gyrus 2 hours ROSC, and APP17 peptide could restorer the expression of PDK, PKB and p- CREB and thereby protect the neurons of hippocampus gyrus from the injury of CPR.
ABSTRACT
Objective To investigate the effect of a peptide,APP17,on regulating the expression of insulin receptor substrate\|1(IRS\|1) and insulin\|like growth factor (IGF\|1R) in neurons of the hippocampus from diabetic mouse. Methods Diabetic mouse models were established by injection of streptozotion.In experimental group,these models were injected with APP17 peptide subcutaneously and their brain sections were taken after 4 weeks of survival. The immunohistochemical stainning of these sections were then performed with IRS\|1 and IGF\|1R antibody.With regard to control groups,the mouse models were only injected saline and gone through the same procedure of immunohistochemistry together with normal mice. Results IRS\|1 and IGF\|1R positive neurons were widely distributed in the hippocampus of the diabetic mice,and the cytoplasm was darkly stained.In the contrast,positive cells in the hippocampus were lightly stained in those normal mice and the APP17 peptide\|treated diabetic mice. Conclusion The expression of IRS\|1 and IGF\|1R could increase in the hippocampus of dabetic mice.The APP17 can regulate the distribution of IRS\|1 and IGF\|1R in the brain of diabetic mice and return them to normal situation.
ABSTRACT
Objective To investigate the effect of the peptide APP17 on regulating the expression of Bcl\|2,Bax,cAMP response element binding Protein(CREB),Ser\|Thr kinase B/protein kinase B(Akt/PKB),apoptosis inducing factor(AIF) in neurons of the hippocampus from the D\|gal mouse. Methods D\|gal mouse models were established by injection of D\|gal.In experimental group,these models were injected with APP17 petide subcutaneously and their brain sections were taken after 3 months of survival.The immunohistochemical staining of these sections was then performed with Bcl\|2,Bax,CREB,Akt,AIF antibody. Results Bax,AIF positive neurons were widely distributed in the hippocampus of the D\|gal mice,and the cytoplasm was darkly stained.In contrast,positive cells in the hippocampus were poorly stained in those normal mice and the APP17 peptide\|treated D\|gal mice.But Bcl\|2,CREB,AKt positive neurons were widely distributed in the hippocampus of those normal mice and the APP17 peptide\|treated D\|gal mice,and the cytoplasm was darkly stained.In contrast,positive cells in the hippocampaus were poorly stained in the D\|gal mice.Conclusion\ The expression of Bax and AIF could be increased in the hippocampus of D\|gal mice.But the expression of Bcl\|2,CREB,AKt decreased in the hippocampus of D\|gal mice.The APP17 can regulate the distribution of Bcl\|2,Bax,CREB,Akt,AIF in the brain of D\|gal mice and return them to normal situation.\;[
ABSTRACT
Objective To investigate the effect of insulin signaling pathway on neuronal survival and the effect of the peptide App17 on regulating the expression of some apoptosis-related proteins in neurons of the hippocampus through intracerebrorentricular injection of streptozotocin in rats. Methods The rats were injected with App17 peptide subcutaneously three weeks after the model group was established by intracerebrorentricular injection of streptozotocin.After the four-week treament,the expressions of the apoptosis-related proteins,such as Bcl-2,Bax,CytoC in neurons of the hippocampus were tested with immunohistochemical staining and Western blotting.Results Bax,CytoC positive neurons were widely distributed in the hippocampus of the model group,and the cytoplasm was darkly stained.In contrast,the positive neurons for Bax,CytoC in hippocampus were poorly stained in the control group and the treated group,and appeared significant difference in cell counting as compared with model group.Bcl-2 positive neurons were widely distributed in the hippocampus in the control group and the treated group,and the cytoplasm was darkly stained while its positive neurons were poorly stained in the model group,and appeared significant difference in cell counting as compared with the model group.From the Western blotting clear bars could be seen in the three groups and there was a significant difference between them.Conclusions The expression of Bax,CytoC increased in the hippocampus in the rats with intracerebrorentricular injection of streptozotocin while the expression of Bcl-2 decreased.The App17 peptide could promote the rehabilitation of the abnormal expression of the three proteins to some extent.The insulin signaling pathway could affect the survival of the neurons in rats' hippocampus.
ABSTRACT
Objective Through the observation on the distribution of hyperphosphorylated Tau,to investigate the connection between hyperphosphorylated Tau and learning, memory tasks. Furthermore, the treatment of App17 on brain tissues of diabetic mice. Methods Diabetic model mouse was produced in the use of streptozotion and App17 peptide as a curative was injected subcutaneously. Four weeks later, removed the brains. Immunohistochemical stainning was done with AT\|8, Tau\|1, again with Tau\|1 antibody after dephosphorylation. Results In the brains of diabetic mice positive AT\|8 reacting neurons were widely distribution in retrosplenial granular cortex, hippocampas, thalamus et al, the cytoplasm was darkly stained, while in normal mice and App17 peptide\|treated diabetic mice positive cells were localized in retrosplenial granular cortex, however, in hippocampas and RSG area, the cytoplasm were poorly stained. Conclusion Hyperphosphorylated Tau is widely expressed in brains of diabetic mice. App17 peptide can improve the hyperphosphorylated Tau in brains of diabetic mice, therefore, it may improve learning ability and memory.\;