Effect of herbal formula GAPT on cholinergic system in mice with scopolamine?induced memory impairment / 中国实验动物学报

Objective To investigate the effect of a Chinese medicine formula GAPT, a combination containing Chinese herbs ginseng,Acorus tatarinowii, Polygala and tuber curcuma, on the behavior and cholinergic system in mice with scopolamine-induced memory impairment, and to explore the neuroprotective mechanism of GAPT. Methods ICR mice were randomly divided into normal control group(solution of 0.5% carboxy methyl cellulose, CMC), model group (0.5% CMC),positive control group(donepezil, 0.92 mg/(kg·d)), GAPT high, medium and low dose groups(20 mg/(kg·d),10 mg/(kg·d),5 mg/(kg·d)),18 mice in each group, were given intragastric gavage once a day for 30 days. After the last administration,the control group and model group received intraperitoneal injection of normal saline,and the other groups intraperitoneal injection of scopolamine(3 mg/(kg·d)), dissolved in 0.9% normal saline. Morris water maze test was performed to assess the learning and memmory ability. Then the mice were killed and the Ach content and AchE and ChAT activity in the cortex and hippocampus were detected. Results GAPT increased the swimming dis-tance,swimming time and the residence time in target quadrant of the model mice,increased the content of Ach and the ac-tivity of ChAT,and decreased the activity of AchE in the brain of the model group. Conclusions GAPT can improve the learning and memory ability of mice induced by scopolamine,and its mechanism may be related to cholinergic system.

Preliminary discussion on the effects of guanosine, curcumin on learning and memory in AD double transgenic mice / 中国实验动物学报

Objective Using Morris water maze test to evaluate the effects of guanosine and curcumin on cognitive function of APPswe/PS1dE9 double transgenic mice .Methods 3-month old APPswe/PS1dE9 dtg mice were randomly di-vided into model group , donepezil HCL group , guanosine group , curcumin group , curcumin and guanosine group ( n=12), with age-matched Wild C57BL/6J mice of the same genetic background as normal control group .Medication was giv-en once a day for 1 month.Using Morris water maze to test the spatial learning and memory ability of mice .Results Guanosine and curcumin could improve spatial learning and memory disorders of AD mice , particularly in the group of cur-cumin.Conclusion Guanosine and curcumin improve the cognitive ability of APPswe /PS1dE9 double transgenic mice with early cognitive impairment .

Effect of curcumin on synapse-related protein expression of APP/PS1 double transgenic mice / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of curcumin on the expression of synapse-related proteins PSD-95 and Shank1 in APP/PS1 double transgenic mice.</p><p><b>METHOD</b>Three-month-old APP/PS1 dtg mice were randomly divided into the model group, the positive Rosiglitazone control group and curcumin high (400 mg x kg(-1) x d(-1)), medium (200 mg x kg(-1) x d(-1)) and low (100 mg x kg(-1) x d(-1)) dose groups, with non-genetically modified mice with the same background as the normal group. After the oral administration for three months, immunohistochemistry and Western blot were adopted for detection.</p><p><b>RESULT</b>According to the behavioral detection, the treatment group and the model group showed differences in the place navigation test and the spatial probe test to varying degrees (P < 0.01 or P < 0.05). The expression of PSD-95 and Shank1-positive cells of hippocampus CA1 region significantly decreased in model mice compared with normal control group (P < 0.01); while the curcumin intervention group showed recovery to some extend. Western blot results showed that the strap of PSD-95 protein expression became significantly thinner and lighter in the model group compared with the normal control group (P < 0.01); while the curcumin intervention group showed notably thicker and darker straps of PSD-95 protein expression (P < 0.05).</p><p><b>CONCLUSION</b>Curcumin can increase the expression of synapse-related proteins PSD95 and Shank1 in APP/PS1 double transgenic mice, improve structure and plasticity of synapse in APP/PS1 double transgenic mice and enhance their learning and memory abilities.</p>

Effect of curcumin on expression of Abeta42 and Abeta-degrading enzyme NEP in APPswe/PS1dE9 double transgenic mice / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of curcumin on the expression of Abeta42 and its degrading enzyme NEP in APP/PS1 double transgenic mice.</p><p><b>METHOD</b>3-month old APP/PS1 dtg mice were randomly divided into model group, positive control group and curcumin large, medium and small dose group. After 3 months, Morris water maze, immunohistochemistry, Western blot were applied to detect learning and memory ability of animal.</p><p><b>RESULT</b>Behavior detection, compared with the model group, treatment group showed varying degrees of difference in place navigation test and space exploration experiments (P < 0.01 or P < 0.05). The expression of Abeta42 and its degrading enzyme NEP, Abeta42-positive cells of hippocampus CA1 region significantly increased in model mice as compared with normal control group (P < 0.01).</p><p><b>CONCLUSION</b>Curcumin can improve learning and memory ability of APP/PS1 double transgenic mice through increasing the expression of Abeta-degrading enzyme NEP and decreasing the expression of Abeta42.</p>

Neuroprotective effects of curcumin / 中国中药杂志

Traditionally, turmeric has been put to use as a food additive and herbal medicine in Asia. Curcumin is an active principle of the perennial herb curcuma longa (commonly known as turmeric). Recent evidence suggests that curcumin has activities with potential for neuroprotective efficacy, including anti-inflammatory, antioxidant, and antiprotein-aggregate activities. In the current review, we provide the newly evidence for the potential role of curcumin in the neuroprotective effects of neurodegenerative diseases like Alzheimer's disease (AD).

Characteristics and Application of Transgenic Mouse Models of Alzheimer's Disease / 中国实验动物学报

The aim of establishment of animal models is to replicate human diseases in the animals and serve studies on causes, symptoms, pathogenesis, diagnosis and treatment, etc. of those diseases. Up to now, there is no ideal animal model of Alzheimer's disease(AD). The lag of animal models of Alzheimer's disease (AD) has greatly restricted the studies on of AD-related drug development. Regarding the causes and mechanisms of AD, some more desirable AD animal models have been developed. In recent years, some transgenic AD animal models have emerged and much facilitate the studies on etiology and pathogenesis of AD. However, this model can not replicate all the features of AD. The most striking distinction is a lack of neurofibrillary tangles (NFTs), and in some types of transgenic models (especially single transgenic models), no extensive neuronal loss is observed. Although tau protein has been detected in those models by immunohistochemical methods, paired helical filaments (PHF) have never been found. In this article, we are trying to review on some hot topics of development and application of transgenic mouse models in AD research.

Study on Blood-stasis Syndrome Induced by Cold: Target on the Tongue / 中国实验方剂学杂志

Objectives:To observe the changes of the tongues in rats with blood-stasis syndrome induced mainly by cold. To explore the evidence that tongues were the target of blood stasis syndrome and the target of medication. Methods: Rats with blood-stasis syndrome induced by cold (BSC group) were dipped into ice water (0 ℃) for 5 minutes every day and lasted 20d individually. Different drugs were given orally after the model establishment. And then we took photos of tongues of all rats by digital camera, analyzed the gray scale value of all rats' tongues using image analysis software, and observed the capillaries in tongues by electron microscope. Results: The tongues of rats which had been frozen in ice water for 20 d (once a day) were dark purple, the same as that of models induced by chemical materials .While as for the normal rats, the tongues were lustrous and ruddy. The changes of color of the tongues persisted about 1 week and were great obvious at the 3rd day after the model establishment among different time-points. After given different drugs, the degree of dark purple tongue degraded, showed significant difference (P < 0.01) from that of model rats. The capillary stegnosis and nucleus turgescence of vascular endothelial cell were observed in tongues in BSC group by using electron microscope. After medication, the above changes recovered. Conclusion: The degree of dark purple tongue indicates the degree of diseases with blood-stasis syndrome. The tongue probably is a target of drug treatment.

Effect of GEPT extracts on spatial learning ability of APPV717I transgenic mice at early stage of dementia and its possible mechanism / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of GEPT extracts on spatial learning ability of the APPV717I transgenic mice at the early stage of dementia and its possible mechanism.</p><p><b>METHOD</b>Thirty APPV717I transgenic mice were randomly divided into three GEPT groups by intragastric administration at doses of 0.075, 0.15, 0.3 g x kg(-1) x d(-1), and a donepezil group by intragastric administration of 0.92 mg x kg(-1) x d(-1), a APPV717I transgenic model group and a normal group by intragastric administration of distilled water. A four-month treatment regimen with GEPT extracts was administered to APPV717I transgenic mice. Results showed that Spatial memory ability was measured in Morris water maze. The total area covered by shank1 and integral optical density in CA1 subfield within the hippocampus were determined using immunohistochemical stains and Image-Pro plus analysis. The ultrastructure of synapses in the hippocampal CA1 region was observed by electronic microscope.</p><p><b>RESULT</b>After a four-month of GEPT treatment regimen, the mean escape latency period were significantly shortened (P < 0.05), and the target quadrant search time were significantly increased (P < 0.05) compared to the APPV717I transgenic model mice. There was a significant higher level in the expression of shank1 detected in the hippocampal CA1 area of APPV717I transgenic mice associated with an increase in the number of synapses treated with GEPT than the levels in the APPV717I transgenic model mice alone. The total area of positive cells covered by shank1 and their integral optical density in the hippocampal CA1 area of the APPV717I transgenic mice treated with GEPT were significantly increased more than those of the APPV717I transgenic model mice.</p><p><b>CONCLUSION</b>GEPT extracts can obviously improve the spatial memory ability of APPV717I transgenic mice at the early stage of dementia through enhancing the number of synapses and the expression of shank1, and this might lead to development of novel treatment therapies for the memory loss associated with AD.</p>

An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)" / 中西医结合学报

In order to provide the "guiding principles of clinical research on mild cognitive impairment (MCI) (protocol)" edited by Beijing United Study Group on MCI of the Capital Foundation of Medical Developments (CFMD) with evidence support, clinical criteria, subtypes, inclusion and exclusion of MCI, and use of rating scales were reviewed. The authors suggested that MCI clinical criteria and new diagnosis procedure from the MCI Working Group of the European Alzheimer's disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Diagnostic rating scales including Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Instrumental Activities of Daily Living (IADL) are very useful in definition of MCI but can not replace its clinical criteria. Absence of major repercussions on daily life in patients with MCI was emphasized, but the patients may have minimal impairment in complex IADL. According to their previous research, the authors concluded that highly recommendable neuropsychological scales with cut-off scores in the screening of MCI cases should include Mini-Mental State Examination (MMSE), logistic memory test such as Delayed Story Recall (DSR), executive function test such as Clock Draw Test (CDT), language test such as Verbal Category Fluency Test (VCFT), etc. And finally, the detection of biological and neuroimaging changes, including atrophy in hippocampus or medial temporal lobe in patients with MCI, was introduced.

Guiding principles of clinical research on mild cognitive impairment (protocol) / 中西医结合学报

Mild cognitive impairment (MCI), as a nosological entity referring to elderly people with MCI but without dementia, was proposed as a warning signal of dementia occurrence and a novel therapeutic target. MCI clinical criteria and diagnostic procedure from the MCI Working Group of the European Alzheimer's Disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Beijing United Study Group on MCI funded by the Capital Foundation of Medical Developments (CFMD) proposed the guiding principles of clinical research on MCI. The diagnostic methods include clinical, neuropsychological, functional, neuroimaging and genetic measures. The diagnostic procedure includes three stages. Firstly, MCI syndrome must be defined, which should correspond to: (1) cognitive complaints coming from the patients or their families; (2) reporting of a relative decline in cognitive functioning during the past year by the patient or informant; (3) cognitive disorders evidenced by clinical evaluation; (4) activities of daily living preserved and complex instrumental functions either intact or minimally impaired; and (5) absence of dementia. Secondly, subtypes of MCI have to be recognized as amnestic MCI (aMCI), single non-memory MCI (snmMCI) and multiple-domains MCI (mdMCI). Finally, the subtype causes could be identified commonly as Alzheimer disease (AD), vascular dementia (VaD), and other degenerative diseases such as frontal-temporal dementia (FTD), Lewy body disease (LBD), semantic dementia (SM), as well as trauma, infection, toxicity and nutrition deficiency. The recommended special tests include serum vitamin B12 and folic acid, plasma insulin, insulin-degrading enzyme, Abeta40, Abeta42, inflammatory factors. Computed tomography (or preferentially magnetic resonance imaging, when available) is mandatory. As measurable therapeutic outcomes, the primary outcome should be the probability of progression to dementia, the secondary outcomes should be cognition and function, and the supplement outcome should be the syndrome defined by traditional Chinese medicine. And for APOE epsilon4 carrier, influence of the carrier status on progression rate to dementia and the effect of treatment should be evaluated.

Effects of amyloid beta protein precursor 17 peptide on distribution of insulin receptor substrate-1 in brain and degeneration of neurons in hippocampus of diabetic mice / 中国组织工程研究

BACKGROUND: In brain insulin does its work through the insulin receptor substrate (IRS). Amyloid beta protein precursor 17 (APP17) peptide has the neurotrophic function, which may improve diabetic encephalopathy resulted from insulin deficiency by affecting insulin receptor substrate.OBJECTIVE: The mouse diabetic model was produced to observe the effect of APP17 peptide on the distribution of IRS-1 in brain tissues.DESIGN: Randomized control animal experiment.SETTING: Staff Room of Pathology, College of Basic Medical Sciences,Capital University of Medical Sciences; Beijing Research Laboratory for Brain Aging of Xuanwu Hospital.MATERIALS: The experiment was performed in Staff Room of Pathology,College of Basic Medical Sciences, Capital University of Medical Sciences and Beijing Research Laboratory for Brain Aging of Xuanwu Hospital from September to October 2003. Totally 18 male kunming mice were employed,and randomly assigned into control group, diabetic group and APP17 peptide treatment group with 6 mice in each group.METHODS: ①The mice were subjected to intraperitoneal injection of streptozotocin (STZ, Sigma) by 200 mg/kg, and 3 days later, the tail blood was sampled to examine non-fasting blood glucose, and the blood glucose over 15 mmol/L was set as the criteria for successful diabetic model establishment. ②In APP17 + diabetes mellitus group, the mice received subcutaneous injection of 0.35 μg APP17 peptide once daily for 2 weeks. The mice in the normal control group were not interfered. ③Then brain was removed and crystat sections were prepared. Immunohistochemical staining was done for IRS-1 at four weeks after giving streptozotocin.MAIN OUTCOME MEASURES: Pattern and distribution of IRS-1 positive cells of mice in each group.RESULTS: Totally 18 mice were involved in the result analysis. ①In the brains of diabetic mice the IRS-1 immunohistochemical positive cells distributed at cortex, hippocampus, thalamus, hypothalamus and so on, while the positive cells distributed only at cortex and hippocampus in the normal control group and APP17 peptide treatment group, lightly stained. ②Numbers of immunohistochemical positive cells of IRS-1 of cerebral hippocampus in the diabetic group, normal control group and APP17 peptide treatment group were (28.7±1.5), (9.2±1.5), (10.1±1.4) piece per 10 power object lens, and that in the diabetic group was higher than that in the other two groups (P ＜ 0. 001 ). CONCLUSION: Neurons in many regions of brains of diabetic mice have plenty of IRS-1 positive cells. APP17 peptide can make part and quantity of IRS-1 positive cells normality so as to ameliorate the degeneration of hippocampal neurons of diabetic mice.

Effect of APP17 peptide and jiunao yizhi capsule on expression of protein phosphatase 1 in hippocampus of aging mice induced by D-galactose / 中国组织工程研究

BACKGROUND: D-galactose-induced aging animal model is similar tohuman natural aging. Whether the expression of protein phosphatase-1(PP-1) in the brain of D-galactose-induced aging mice is related to cerebralaging process or not should be researched further. OBJECTIVE: To investigate the effect of the APP17 peptide and theliquid extract ofjiunao yizhi capsule on regulating the expression of PP-1 inhippocampal neurons of the aging mice induced by the D-galactose (D-gal). DESIGN: A random controlled study. SETTING: Department of Pathology, College of Basic Medical Sciences, Capital University of Medical Sciences and Beijing Research Laboratory forBrain Aging, Xuanwu Hospital of Capital University of Medical Sciences. MATERIALS: The study was completed between July 2003 and July2004 in the Experimental Center of Capital University of Medical Sciences. Forty male Kunming mice (SPF grade) with a body mass fron 28 g to 32 gwere purchased from Chinese Academy of Medical Sciences Institute ofMaterial Medical.METHODS: Kunming mice were randomly divided into 5 groups: control group, D-gal group, APP17 peptide treatment group, low dose herb treatment group, and high dose herb treatment group with 8 mice in each group. In Dgal group, APP17 peptide treatment group, low dose herb treatment group and high dose herb treatment group, galactose was injected subcutaneously (50 nmg/kg). Meanwhile, 0.1 mL normal saline containing 0.35 μg of APP17 peptide was injected subcutaneously into the mice in APP17 peptide treatment group, once a day for 3 months; liquid extract of jiunao yizhi capsule (provided by Beijing Chaoyangmen Hospital and Shanxi Quwo Traditional Medical Institute; the main component: dangshen, baizhu, guijia and chuanshanjia, etc.) was perfused by stomach (0.3 g/kg and 1.0 g/kg respectively) in low dose herb treatment group and high dose herb treatment group, once a day. And equivalent normal saline was injected and perfused in the two control groups. After 3 months of survival, the mice were killed and their brains were cut into sections. The immunohistochemical staining of these sections was then performed with PP-1 antibody.MAIN OUTCOME MEASURES: The results of immunohistochemical staining analysis of PP-1.RESULTS: Forty mice entered the final analysis without any loss. PP-1 positive cells in the hippocampus were poorly stained in the D-gal mice. In contrast, PP-1 positive neurons were widely distributed in the hippocampus of those normal mice, the APP17 peptide-treated D-gal mice and the high liquid extract of raw herb-treated D-gal mice. These cells were darkly stained in cytoplasm. The unexpected result was that in the low liquid extract of raw herb-treated D-gal mice the number of PP-1 positive neurons did not increase to normal.CONCLUSION: The results demonstrated that the expression of PP-1 decreased in the hippocampus of D-gal mice. The APP17 and low dose liquid extract of raw herbs can regulate the distribution of PP-1 in the brain of D-gal mice and make them recover to normal situation.

Improved effect of APP17 peptide on overexpression of phosphorylated Tau protein in brain tissues of mice with diabetes mellitus / 中国组织工程研究

BACKGROUND: Overexpression of phosphorylated Tau protein is a factor of dementia, and scholars abroad find that APP17 peptide may have effect on it.OBJECTIVE: To observe changes of phosphorylated Tau protein Ser202/Thr205 of mice with diabetes mellitus (DM) after injection of APP17 peptide.DESIGN: Randomized control study.SETTING: Department of Pathology, Capital University of Medical Sciences; Department of Brain Aging, Xuanwu Hospital, Capital University of Medical Sciences.MATERIALS: The experiment was carried out in the Pathological Department of Capital University of Medical Sciences and Brain Aging Department of Beijing Xuanwu Hospital. A total of 18 male Kunming mice of 8 weeks old and weighing 28-32 g were randomly divided into control group, DM group and APP17 peptide group with 6 in each group.METHODS: DM models were induced by streptozotocin (STZ) through selectively destroying β-islet cells; meanwhile, APP17 peptide was intraperitoneally injected into mice. Four weeks later, brain tissue underwentimmunohistochemical staining with AT-8 (Ser202/Thr205, a special monoclonal antibody).MAIN OUTCOME MEASURES: ① Morphological observation; ② AT-8 distribution; ③ quantitative analysis of immunohistochemical staining.RESULTS: Positive AT-8 cells in DM group were distributed in retrosplenial cortex, hippocampus, thalamus, hypothalamus, etc.; however, those incontrol and APP17 peptide groups were only distributed in retrosplenial cortex and hippocampus, and poorly stained.CONCLUSION: Positive AT-8 cells may be widely distributed in neurons of brains of DM mice; however, APP17 peptide may normalize the expression of positive AT-8 cells.

THE ROLE OF APP17 ON MODULATION OF IRS-1 AND IGF-1R EXPRESSIONS IN HIPPOCAMPAL NEURONS OF DIABETIC MICE / 解剖学报

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.

THE EFFECT OF APP17 ON MODULATION OF Bcl-2,Bax,CREB,AKt,AIF EXPRESSIONS IN HIPPOCAMPAL NEURONS OF D-GALACTOSE INDUCED BRAIN AGING OF THE MICE / 解剖学报

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.\;[

EFFECT OF STZ INTRACEREBRORENTRICULAR INJECTION ON EXPRESSIONS OF APOPTOSIS-ASSOCIATED PROTEINS IN HIPPOCAMPAL NEURONS OF RATS / 解剖学报

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.

THE EFFECT OF App17 PEPTIDE ON THE EXPRESSION OF HYPERPHOSPHORYLATED Tau PROTEIN / 解剖学报

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.\;