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OBJECTIVE: To examine whether ginsenoside Rg1 (Rg1) inhibits the high-voltage-activated calcium currents (ICa,HVA) via mitogen-activated protein kinase (MAPK) in hippocampal neurons in rat brain slices exposed to beta-amyloid peptide 25-35 (Aß25-35). METHODS: An experimental Alzheimer disease (AD) model was prepared by exposure of rat brain slices to Aß25-35 (10 µmol/L). After treatment with Rg1 (20 µmol/L), the ICa,HVA elicited in hippocampal neurons in these rat brain slices upon depolarization from-40 to 40 mV for 200 ms was recorded by a whole-cell patch clamp to analyze the changes in the peak current density, I-V curve, activation-V curve, and inactivation-V curve. RESULTS: Exposure of rat brain slices to Aß led to a significant increase in ICa,HVA, enhancement of the voltage sensitivity of channel activation, and reduction of the voltage sensitivity of channel inactivation in neurons in the hippocampus of rat brain slices. Rg1 treatment significantly inhibited these changes. These effects of Rg1 could be effectively inhibited by the MAPK inhibitor PD98059. CONCLUSION: Rg1 can inhibit Ica,HVA via MAPK in hippocampal neurons in Aß-exposed rat brain slices.
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OBJECTIVE: To observe the effect of a Chinese medicine compound, Naoerkang (NEK), on amyloid-beta peptide (1-42; Aß(1-42)) and matrix metalloproteinase-9 (MMP-9) expressions in the hippocampus of Alzheimer's disease (AD) model rats. METHODS: A total of 48 male Sprague Dawley (SD) rats were randomly divided into normal control, untreated, and piracetam groups, and low-dose, medium-dose, and high-dose NEK groups, with 8 rats in each group. The 5-µL aggregated Aß(1-42) (2 µg/µL) were injected into both CA1 areas of the hippocampus in the rats to establish an AD model, whereas the normal control was treated with the same dose of normal saline. The rats in the NEK groups were treated with a high, medium, or low dose of NEK [60 g/(kg·d), 30 g/(kg·d), and 15 g/(kg·d)], respectively, intragastrically for 28 days; piracetam (0.375 g/kg, intragastrically) was consecutively administered in the piracetam group; and normal saline was applied in the normal control and untreated groups. A Y-maze test was used for behavioral study to test the learning and memory abilities. Aß(1-42) and MMP-9 expressions in the hippocampus was determined immunohistochemically, and the results were analyzed by image acquisition and an analysis system. RESULTS: Aggregated Aß(1-42) induced obvious learning and memory dysfunction, as well as up-regulation of Aß(1-42) expression in the hippocampus. Compared with those in the normal control group, the learning and memory abilities of rats in the untreated group significantly decreased (P<0.01), and the expression of Aß(1-42) was significantly increased (P<0.01). Twenty-eight days after different treatments, compared with those in the untreated group, the learning and memory abilities of AD model rats in the piracetam, low-dose, medium-dose and high-dose NEK groups were significantly improved (P<0.01 or P<0.05), and the expression of Aß(1-42) in the hippocampus decreased (P<0.01 or P<0.05), and MMP-9 increased (P<0.01 or P<0.05), especially in the high-dose NEK group. CONCLUSION: NEK might play a role of anti-dementia by increasing the expression of MMP-9 in the hippocampus of AD model rats, resulting in the reduction of the quantity of Aß(1-42) and improvement in learning and memory ability in AD model rats.
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Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Hipocampo/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Animales , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/enzimología , Región CA1 Hipocampal/patología , Región CA1 Hipocampal/fisiopatología , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/fisiopatología , Inmunohistoquímica , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Memoria/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To investigate the effects of gensenoside Rg1 on expressions of phosphorylated tau protein (P-tau), protein phosphatase 2A (PP2A) and tau protein in Alzheimer's disease-like tau phosphorylation rat brain slices, and to explore the mechanisms of gensenoside Rg1 in inhibiting tau phosphorylation. METHODS: Brains of 5-week-old Wistar rats were cut into slices which were 400 µm thick. These brain slices were randomly divided into blank control group, untreated group, low-dose ginsenoside Rg1 group, medium-dose ginsenoside Rg1 group and high-dose ginsenoside Rg1 group, with 10 slices in each group. All brain slices were cultured with artificial cerebrospinal fluid (ACSF). And brain slices in the ginsenoside R1 groups were administered with ginsenoside Rg1 (60, 120 and 240 µmol/L respectively) in ACSF for 2 h firstly. After 2-hour culture, okadaic acid (OA) was administered into ACSF of the untreated group and the ginsenoside Rg1 groups separately for 3 h to induce tau phosphorylation to prepare AD models. The concentration of OA in each group was 1 µmol/L. There was no any intervention for the brain slices in the blank control group. Expressions of P-tau, PP2A and tau proteins in the brain slices were determined by immunohistochemical method, and the results were analyzed by image acquisition and analysis system. RESULTS: Compared with the blank control group, the expression of P-tau protein was significantly increased (P<0.01) and the expressions of tau and PP2A proteins were decreased (P<0.01, P<0.05) in the untreated group. Compared with the untreated group, the expression of P-tau was significantly decreased (P<0.01) and the expressions of tau and PP2A proteins were increased (P<0.01, P<0.05) in the ginsenoside Rg1 groups, especially in the high-dose ginsenoside Rg1 group. CONCLUSION: Ginsenoside Rg1 can promote dephosphorylation of P-tau by increasing the expression of PP2A in Alzheimer's disease-like tau phosphorylation rat brain slices, so as to inhibit tau phosphorylation.
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Encéfalo/metabolismo , Ginsenósidos/farmacología , Proteínas tau/metabolismo , Animales , Técnicas In Vitro , Masculino , Ácido Ocadaico/efectos adversos , Fosforilación/efectos de los fármacos , Proteína Fosfatasa 2/metabolismo , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To investigate the effects of Naoerkang (NEK), a compound traditional Chinese herbal medicine, on the expressions of beta-amyloid peptide 1-42 (Abeta(1-42)) and neprilysin (NEP) in hippocampal tissues in a rat model of Alzheimer's disease (AD). METHODS: Forty-eight male SD rats were randomly divided into normal control group, untreated group, piracetam group, low-dose NEK group, medium-dose NEK group, and high-dose NEK group, with 8 rats in each group. Five microliters of Abeta(1-42) (2 microg/microL) were injected into CA1 area of hippocampus in rat to establish AD model whereas the normal control rats were injected with same volume of normal saline for comparison. The rats in the NEK groups were treated respectively with high-, medium- and low-dose [60, 30, 15 g/(kg.d)] NEK for 28 days consecutively; piracetam [0.375 g/(kg.d)] was intragastrically administered to rats in the piracetam group; and normal saline was applied in the control and untreated groups. Y-maze test was used for behavioral study to test the learning and memory abilities of rats in different groups. The expressions of Abeta(1-42) and NEP in hippocampus were determined by immunohistochemical method, and the results were analyzed by image acquisition and analysis system. RESULTS: Injection of Abeta(1-42) could induce learning and memory dysfunction and up-regulate Abeta(1-42) expression in hippocampal tissue in rats of the untreated group. Compared with the normal control group, the abilities of learning and memory of rats in the untreated group were significantly decreased (P<0.01) and the expression of Abeta(1-42) was significantly increased (P<0.01) after model establishment. After 28-day administration of NEK and piracetam, the abilities of learning and memory of AD rats in piracetam and low-dose, medium-dose and high-dose NEK groups were significantly improved as compared with the untreated group (P<0.01 or P<0.05); the expression of Abeta(1-42) in hippocampal tissues was decreased (P<0.01 or P<0.05) and the expression of NEP was increased (P<0.01 or P<0.05), especially in the high-dose NEK group. CONCLUSION: NEK can play the role of anti-dementia by increasing the expression of NEP in hippocampal tissues of AD rats so as to reduce the quantity of AAbeta(1-42) and by improving the ability of learning and memory of rats with AD.