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ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.
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Previous studies demonstrate that diabetes mellitus induces cognitive impairment,leading to diabetic encephalopathy(DE), which is closely related with hippocampal synaptic plasticity impairment,including synaptic structural and functional damage. Structural damage mainly embodied in the synapse degeneration.Functional damage mainly reflects in the LTP damage, including the composition variation and functional lesions of N-methyl-D-aspartate receptors(NMDARs), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) and patassium channels.Abnormal synaptic plasticity may be critical in the pathogenesis of diabetic encephalopathy. In this review, we summarized the relationship between DE and synaptic plasticity impairment.
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Objective To investigate the neuroprotective effect and mechanism of liraglutide on diabetic rats. Methods 24 healthy male SPF Goto-Kakizaki (GK) rats with random blood glucose greater than 11.1 mmol/L were selected as the experimental group, and randomly divided into diabetes mellitus group ( n＝12) and liraglutide group (n＝12). Ten healthy male SPF Wistar rats with the same age and weight as GK rats were selected as normal control group. After adaptively feeded for 2 weeks, the liraglutide group was given liraglutide (400 μg·kg－1·d－1, subcutaneous injection), while the control group and diabetes mellitus group were given the same volume of saline, and continued to be administered for 8 weeks. After 10 weeks, data and biochemical indicators were recorded. Effects of liraglutide on learning and memory in diabetes mellitus rats were detected by Morris water maze test. HE staining observed the hippocampal neurons morphology. Western blotting method detected the expression of p- IκB kinase (IKK) β, p-NF-κB, NF-κB, Klotho, and PRX2 in hippocampus. Results Morris water maze test showed that liraglutide can improve the spatial learning and memory ability of diabetes mellitus rats. HE staining showed that liraglutide significantly reduced the pathological damage of hippocampal neurons of diabetes mellitus rats. Western blotting showed that liraglutide inhibited NF-κB signaling pathway in hippocampus of diabetes mellitus rats. The expression of Klotho protein in hippocampus of diabetes mellitus group was significantly lower than that of control group, while the expression of PRX2 protein was higher than control group (t＝8.298,－7.398,all P<0.01). The expression of Klotho and PRX2 protein in hippocampus of liraglutide group were higher than diabetes mellitus group (t＝－13.059, 14.113, all P<0.01). The expression of Klotho protein of liraglutide group was similar to that of control group ( t ＝ －1. 137, P>0. 05 ). The expression of PRX2 protein was significantly higher than control group (t＝－28.055, P<0.01). Conclusions Liraglutide may enhance the expression of antioxidant stress protein including Klotho and PRX2, by inhibiting NF-κB signaling pathway in hippocampus of diabetes mellitus rats, reduced oxidative stress and improved the injury of hippocampal neuronal in diabetes mellitus rats, which seems to play a neuroprotective effect, to prevent and delay the occurrence of diabetic encephalopathy.
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Objective To analyze the changes of metabolites in the left posterior cingulate cortex (PCC)in patients with type 2 diabetes mellitus (T2DM),diabetic encephalopathy(DE)and healthy control(HC),to discuss the pathogenesis and to provide the biological information for the early diagnosis of DE.Methods 46 patients with clinical diagnosis of T2DM and 26 matched HC were received single-voxel MRS on the left PCC using Siemens Verio 3.0T MR scanner.Participants were divided into two groups based on MoCA scoring criteria and diabetic retinopathy,including DM group (n=31)and DE group (n=15).All T2DM patients were received fasting blood glucose,glycated hemoglobin (HbAlc)and other clinical labortory tests before MR scans.SPSS 21.0 software package was used for statistical analysis.Results (1)Ins and Ins/Cr were increased gradually in DE compared with HC and DM groups(P＜0.05).(2) NAA/Ins ratio in DE group was significant lower than that in DM and HC group,but no significant difference was observed between DM and DE groups(P＞0.05).No significant differences exsited in NAA/Cr among these three groups(P＞0.05).Conclusion MRS can be more sensitive to detect DE patients on the left PCC-related metabolic abnormalities and help DE with early screening and preliminary clinical diagnosis.The increase Ins/Cr in the left PCC area is more sensitive to the brain injury of T2DM and can refelect the progress degree.It is necessary to expand the sample size to verify its diagnostic efficacy and early warning of the brain injury.
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Objective:To investigate the relevance between spatial learning and memory impairment and the changes of inducible nitric oxide synthase (iNOS) activity,superoxide dismutase (SOD) activity and malondiadehyde (MDA) content in hippocampus from Type 1 diabetic mice.Methods:Sixty male mice were randomly assigned into a control group (NC group,20 mice) and a Type 1 diabetic group (DM group,40 mice).Type 1 diabetic mouse models were established by a large dose intraperitoneal injection of streptozotocin (100 mg/kg).The spatial learning and memory abilities of mice were assessed by Morris water maze (MWM) test.After MWM test,we chose 20 mice (diabetic encephalopathy mice) with the worst spatial learning and memory abilities from diabetic model group,and detected the iNOS activity,SOD activity and MDA content in hippocampus in both groups.Results:Compared with the NC group,the escape latency was significantly extended and platform crossings were significantly declined in diabetic mice (P＜0.01).Furthermore,the activity of iNOS and the content of MDA were markedly increased,and the activity of SOD was significantly decreased in hippocampus of diabetic encephalopathy mice (P＜0.01).Conclusion:The established Type 1 diabetic mice show symptoms of cognitive dysfunction,which might be related to the increase of oxidative stress in hippocampus.
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This study was designed to investigate the therapeutic effect of novel compound Z-9-octadecenyl-2-propanesulfonamide (N15) on diabetes-associated cognitive decline (DACD). Type 2 diabetes (T2DM) mice models were established with multiple injection of low doses of streptozotocin (STZ) in mice on high fat diet (HFD). Vehicle and different concentrations of N15 (50 and 100 mg·kg-1·d-1) were administrated orally for 6 weeks. The step-down test, dark avoidance task and Morris water maze were conducted at the 6th week. The level of glucose and lactic acid in hippocampus were determined and mRNA of growth associated protein-43 (GAP-43), synaptophysin (SYN), brain derived neurotrophic factor (BDNF) and neurotrophins-3 (NT-3) in hippocampus were analyzed by real time PCR. The beneficial effects of N15 on learning and memory were found in the test of step-down, dark avoidance and Morris water maze. N15 reduced the level of glucose and lactic acid in hippocampus of HFD+STZ-induced diabetic encephalopathy model mice. Additionally, the mRNA expression of GAP-43, SYN, BDNF and NT-3 in hippocampus of HFD+STZ-induced diabetic encephalopathy mice were significantly increased by N15 (P<0.01). These results suggest that the novel compound N15 can ameliorate diabetes-associated cognitive decline and the potential mechanism may be associated with the expressions of increased synaptic-related factors and neurotrophic factor in the hippocampus of diabetesassociated cognitive decline in mice.
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Objective To study the effect and mechanism of endoplasmic reticulum stress on hippocampal neuron apoptosis and cognitive impairment in type 1 diabetic rats. Methods Ten rats were randomly selected as normal control group (Con group) from thirty Wistar rats, and the remaining twenty rats were intraperitoneally injected with streptozotocin to prepared for type 1 diabetic rat model. The successful model rats were randomly divided into diabetic group (DM group) and diabetic +Salubrinal group (DM+Sal group). Rats of DM+Sal group were injected by lateral ventricle with Salubrinal ( 75μmol/L, 1μL). Rats of Con group and DM group were given the equal volume of normal saline. The rat cognitive function was assayed by Morris water maze test. The hippocampal neuron apoptosis was detected by TUNEL and flow cytometry methods. The protein levels of endoplasmic reticulum stress markers, GRP78, CHOP and Caspase12, and the mRNA levels of GRP78 and CHOP, were examined by Western blot assay and Real-time PCR, respectively. Results Compared with the Con group, the cognitive function was significantly decreased in DM group, and the apoptotic rate of hippocampal neurons was increased. The protein levels of endoplasmic reticulum stress markers GRP78, CHOP and Caspase12 were significantly increased (P<0.05), and the mRNA levels of GRP78 and CHOP were also higher in DM group (P<0.05). After the injection with Salubrinal, the cognitive function was improved and hippocampal neuron apoptotic rate was decreased in DM+Sal group compared with those of DM group. Moreover, the protein levels of GRP78, CHOP and Caspase12 were significantly decreased (P<0.05) and the mRNA levels of GRP78 and CHOP were also lowered in DM+Sal group (P<0.05). Conclusion The cognitive impairment and the higher apoptotic rate appear in the diabetic rats, and endoplasmic reticulum stress may play an important role in it.
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Diabetes mellitus can cause central nervous system disorder that is summarized as diabetic encephalopathy, which manifests in cognitive dysfunction and other mental illnesses. Astrocyte, with a huge number and extensive functions, is an important part of the central nervous system. Morphological and functional changes in astrocyte have been observed in diabetes mellitus, which involve the quantity, the expression of neurotransmitters and relative transporters, the activity of enzyme, the storage of glycogen and the intercellular connection and communication.
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Huanglian Wendan decoction (HLWDD) has been used for the treatment of symptom of "Re", one of major causes in diabetes and metabolic disorders, according to the theory of traditional Chinese medicine. The present study aimed at investigating the cerebral protective effects of HLWDD on diabetic encephalopathy (DE), one of the major diabetic complications. The effects of HLWDD and metformin were analyzed in the streptozocin (STZ) + high-glucose-fat (HGF) diet-induced DE rats by gastric intubation. In the present study, the effects of HLWDD on cognition deficits were investigated after 30-day intervention at two daily dose levels (3 and 6 g·kg). To explore the potential mechanisms underlying the effects of HLWDD, we detected the alterations of neuronal damages, inflammatory cytokines, and impaired insulin signaling pathway in hippocampus of the DE rats. Based on our results from the present study, we concluded that the protective effects of HLWDD against the cognitive deficits and neuronal damages through inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus of the DE rats.
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Animals , Humans , Male , Rats , Cognition Disorders , Genetics , Metabolism , Cytokines , Genetics , Metabolism , Diabetic Neuropathies , Drug Therapy , Genetics , Metabolism , Psychology , Drugs, Chinese Herbal , Hippocampus , Metabolism , Insulin , Metabolism , Rats, Sprague-DawleyABSTRACT
Diabetes mellitus can cause central nervous system disorder that is summarized as diabetic encephalopathy, which manifests in cognitive dysfunction and other mental illnesses. Astrocyte ,with a huge number and extensive functions,is an im?portant part of the central nervous system. Morphological and functional changes in astrocyte have been observed in diabetes mellitus , which involve the quantity,the expression of neurotransmitters and relative transporters,the activity of enzyme,the storage of glyco?gen and the intercellular connection and communication.
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O diabetes é um distúrbio complexo e heterogêneo caracterizado por hiperglicemia resultante de defeitos na secreção e ação da insulina. Tem sido reconhecido que, além do comprometimento de órgãos como rins, olhos, fígado e coração, o sistema nervoso central é suscetível aos efeitos deletérios da hiperglicemia em longo prazo. A encefalopatia diabética representa uma das complicações do diabetes, na qual os danos são caracterizados por alterações do funcionamento cognitivo, modificações estruturais e neurofisiológicas no cérebro. Existe uma associação bem reconhecida entre a depressão e o diabetes, uma vez que a prevalência de depressão é maior na população diabética comparada com a população geral. Porém, os mecanismos atribuídos a essa relação ainda estão em fase de investigação. O estresse oxidativo desempenha um papel importante nas complicações do diabetes e pode ser um mecanismo biológico envolvido na relação entre a depressão e o diabetes, relacionado à encefalopatia diabética. Neste artigo de revisão, apresentamos uma visão geral dos principais conceitos relacionados ao assunto, bem como dos dados clínicos e experimentais que suportam a relação entre o dano oxidativo no cérebro e a depressão relacionada com encefalopatia diabética...
Diabetes is a complex and heterogeneous disorder characterized by hyperglycemia resulting from defects in the secretion and action of insulin. It has been recognized that, in addition to the involvement of organs such as kidney, eye, liver, and heart, the central nervous system is susceptible to the deleterious effects of hyperglycemia in the long term. Diabetic encephalopathy is one of the complications of diabetes, in which the damage is characterized by changes in cognitive functioning, structural and neurophysiologic changes in the brain. There is a well-known association between depression and diabetes, since the prevalence of depression is higher in the diabetic population compared to the general population. However, the mechanisms assigned to this relationship are still under investigation. Oxidative stress plays an important role in the complications of diabetes and can be a biological mechanism involved in the relation between depression and diabetes related to diabetic encephalopathy. This review article is an overview of key concepts related to the subject, as well as of the clinical and experimental data supporting the relationship between oxidative damage in the brain and depression related to diabetic encephalopathy...
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Humans , Brain Diseases , Depressive Disorder , Diabetes Complications , Oxidative StressABSTRACT
Objective To investigate the effect of aspirin (Asp) on cognitive function and the insulin-like growth factor-1 receptor/phosphorylated insulin-like growth factor-1 receptor (IGF-1R/p-IGF-1R) expression in the hippocampus of rats with diabetic encephalopathy, so as to analyze the protective mechanism of aspirin on brain. Methods Diabetes mellitus (DM) was induced by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg body mass). Rats were randomly assigned to four groups (n = 10 animals per group), i. e. control, control + Asp, DM, and DM + Asp groups. One week after the injection of STZ, the animals in Con + Asp and DM + Asp groups were gavaged with aspirin (10 mg/ [kg · d]) for 14 weeks. Meanwhile, the control group received the same dose of noromal saline for 14 weeks, and then the cognitive function was observed by Morris water maze (MWM) test in all rats. The expressions of IGF-1R and p-IGF-1R proteins in the hippocampus of rats were examined by Western blotting analysis. Results The cognitive function of diabetic rats was improved after treated with aspirin; the escape latency of MWM test in DM + Asp group was significantly shorter than that in DM group (P< 0.01) ; the number of platform crossing and time spent in the target quadrant in the MWM test were significantly more in DM + Asp group compared with those in DM group (P<0.01 or P<0.05). H-E result showed that the neurons in DM + Asp group were increased compared with that in DM group. The hippocampal expression of p-IGF-1R protein in DM group was significantly lower than that in the control group (P<0.01) and aspirin treatment significantly increased p-IGF-1R expression (P<0.01). However, the IGF-1R protein levels in the hippocampus showed no significant difference between different groups. Conclusion Aspirin may protect the brain of rats with diabetic encephalopathy by regulating the IGF-1R signaling pathway.
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To evaluate the effects of ginseng aqueous extract on learning and memory abilities and neurochemicals in diabetic encephalopathy rat brain. Diabetes mellitus model was established. Cognitive abilities were evaluated with Morris water maze test by the indexes of escape latency time ( ELT) , times of passing through the target area and the percent of swimming track in goal quadrant. We applied online MD-LC-MS/MS method to determine eight neurochemicals in rat hippocampus among different groups in MRM mode. Venusil C18 column was used for separation. Treatment with ginseng aqueous extract significantly improved the cognitive abilities of diabetic rats (p0. 99). The accuracy and precision could meet the analysis requirement. Comparing with the model group, the concentrations of taurine and acetylcholine were significantly increased ( p<0 . 01 ) after treated with ginseng aqueous extract, but the glutamic acid, aspartic acid,γ-aminobutyric acid, serine, dopamine and serotonine decreased dramatically. Ginseng aqueous extract can efficiently regulate the levels of eight neurochemials in diabetic rat brain to normal.
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Objective To investigate the effect of plasma homocysteine (Hcy) levels and cognitive dysfunction on patients with type 2 diabetes and explore the other factors that affect cognitive function.Methods 80 patients with type 2 diabetes were selected as our subjects and they were divided into cognitive impairment group (38 cases),cognitive normal group (42 cases) according to a simple mental state scale(MMSE) score.The plasma Hcy,glycosylated hemoglobin,blood lipid,uric acid,24 h urine trace albumin were measured.Results Plasma Hcy concentration in diabetic cognitive dysfunction,non cognitive impairment group and normal control group respectively were(19.56 ± 5.23),(16.21 ± 3.27),(14.67 ± 4.27) tmol/L,and there was statistically significant difference(F =3.76,P ＜0.05).The plasma Hcy levels in diabetic cognitive impairment group was higher than that non-cognitive impairment group(P ＜ 0.05) and normal control group (P ＜ 0.01),The factors impaired cognitive function in patients with other factors included age,glycosylated hemoglobin,body mass index,diabetes duration and plasma Hcy levels,and there were negative correlation with MMSE score (r =-0.336,-0.285,-0.226,-0.392,-0.312 ; all P values were less than 0.05).Conclusion Patient's age,duration of diabetes,glycosylated hemoglobin and BMI can affect cognitive function in patients.Higher Hcy levels in patients with type 2 diabetes is a risk factor for cognitive impairment.
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Objective: To investigate the relation of diabetic encephalopathy with oxidative stress and hippocampus expression of inducible nitric oxide synthase(iNOS) in rats and to study the therapeutic effects of curcumin. Methods: Diabetes mellitus was induced by injection of Streptozotocin in rats. The experiment animals were randomly divided into control group, diabetic group, diabetes plus curcumin group and control plus curcumin group; animals in the latter two groups received 60 mg·kg-1·d-1 curcumin treatment. Superoxide dismutase(SOD), catalase(CAT), malondialdehyde(MDA) and nitric oxide (NO) in the hippocampal tissues were measured 12 weeks after treatment. The expression of iNOS mRNA and the mean optical density (MOD) of immunoreactive neurons were evaluated by RT-PCR and immunohistochemistry method, respectively. Results: Compared with the control group, diabetic group had significantly lower activities of SOD and CAT, higher contents of NO and MDA, and increased expression of iNOS mRNA and protein in the hippocampal tissues (P<0.01). Compared with the diabetic group, diabetic plus curcumin group had significantly higher activities of SOD and CAT, lower contents of NO and MDA and decreased expression of iNOS mRNA and the MOD of immunoreactive neurons in hippocampus (P<0.01). Conclusion: Diabetic encephalopathy is associated with oxidative stress and increased expression of iNOS; curcumin may protect diabetic encephalopathy by inhibiting oxidative stress and down-regulating the iNOS expression.
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AIM: To investigate the protective mechanism of extract of Ginkgo biloba (EGB) on apoptosis of hippocampus neuronal cells in type 1 diabetic encephalopathic rats. METHODS: Thirty-six male Sprague-Dauley rats were divided into 3 groups: control group, diabetic group and EGB-treated group. Streptozotocin was injected intraperitoneally to the animals in later two groups to induce diabetes. The rats in EGB-treated group were injected intraperitoneally with EGB, and the same volume of normal saline was injected to the rats in other groups. At the end of the 12th week, the spatial learning and memory abilities of rats in each group were examined by Morris water maze test. Blood glucose and serum insulin concentration were measured. The neuron densities in hippocampus were measured by Image-Pro Plus 6.0 software. The expressions of Bax, Bcl-2, caspase-3 were assayed by Western blotting and immunohistochemistry. RESULTS: Compared to control group, the level of blood glucose (P<0.01), the protein expression of Bax (P<0.01) and caspase-3 (P<0.01) in hippocampus neuronal cells, and the ratio of Bax/Bcl-2 (P<0.01) and the escape latency (P<0.01) in diabetic group, were significantly increased, while the serum insulin concentration (P<0.01), the neuronal density (P<0.05) in CA1,CA2 hippocampal regions and the platform searching score (P<0.01) were significantly deceased. After treated with EGB, the serum insulin concentration (P<0.05), the neuronal density (P<0.05) in CA1,CA2 hippocampal regions and the platform searching score (P<0.01) were significantly increased, while the level of blood glucose (P<0.01), the protein expression of Bax (P<0.05), caspase-3 (P<0.05) in hippocampus neuronal cells, the ratio of Bax/Bcl-2 (P<0.01) and the escape latency (P<0.05) were significantly deceased than those in diabetic group. The protein expression of Bcl-2 in hippocampus neuronal cells did not alter in any experimental rats. CONCLUSION: EGB improves the spatial learning and memory capacity in diabetic rats by decreasing the expression of Bax, Bax/Bcl-2 ratio and down-regulating caspase-3 to reduce neurocyte apoptosis and increase the neuron density in CA1, CA2 hippocampal regions, suggesting that effective regulation of neuron apoptosis associated genes may be one of the mechanisms for EGB to treat diabetic encephalopathy.
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Objective To study the relation between diabetic rat encephalopathy and hippocampal apoptosis, and the therapeutic effect and mechanism of Ginkgo biloba extract. Methods Sixty rats were assigned into control group(NC), diabetic encephalopathy group (DM+B) and EGb-treatment group (EGb) randomly, and every group was further divided into two time points of 1 month (NC_1 ,DM+B_1, EGb_1 ) and 3 month(NC_3 ,DM+B_3, EGb_3 ). The behavioral abnormalities were investigated by water maze test and the apoptosis levels of brain tissue by ELISA. Immunohistochemistry and RT-PCR were performed to determine the protein and mRNA expressions of Bcl-2 and Bax. Results (1) Mild dysfunction of learning and memory was detected in DM+B_1 group, and the dysfunction became worse in DM+B_3 group. The matters were greatly improved in EGb-treatment groups. (2) The expressions of Bcl-2 protein and mRNA were increased in DM+B_1 and DM+B_3 groups, and were stronger in EGb_1 and EGb_3 groups. (3) The expressions of Bax protein and mRNA were obviously increased in DM+B_1 and DM+B_3 groups, and were dramatically reduced in EGb_1 and EGb_3 groups. (4) Compared with control group, the apoptosis level of brain tissue was increased in DM+B_1 group, and obviously greater in DM+B_3 group. In the EGb-treatment groups the levels were dramatically reduced. Conclusions Diabetic encephalopathy may be closely related to hippocampal apoptosis. EGb has an protective effect and the mechanism may be attributed to its effects inhibiting apoptosis.
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The purpose of the present work is to observe whether Tau protein Ser202/Thr205 is hyperphosphorylated in braintissues of diabetic mice and to study the effect of App17 peptide. Mouse diabetic model was produced with streptozotocin, andApp1 7 peptide as a treatment was injected subcutaneously into diabetic mice. Four weeks later, fixative was injected intravascu-larly into the mice, the brain was removed and crystat sections prepared. Immunohistochemical staining was done with AT-8. Inthe brains of diabetic mice positive AT-8 reacting neurons were numerous, darkly stained, and widely distributed in retrosplenialgranular cortex, hippocampus, thalamus et al. , while in normal mice and App17 peptide-treated diabetic mice positive cells werescarce and poorly stained. Tau protein is hyperphosphorylated at Scr202/Thr205 site and widely distributed in the brains of dia-betic mice, while App17 peptide can normalize the expression of AT-8 positive cells.
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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.
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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.\;