1.Effect of dopamine receptor agonist apomorphine on scopolamine induced memory deficits in mice.
Hui-Di YANG ; Zheng YANG ; Tao-Di LIU
Chinese Journal of Applied Physiology 2014;30(3):259-263
OBJECTIVETo research the mechanism of dopamine (DA) controlled memory in mice.
METHODSMice received i.p. injection of scopolamine (0.3 mg/kg, SCOP 0.3, and 3.0mg/kg, SCOP 3.0, respectively, n = 10) and saline (NS, n = 10) for 60 days in experiment 1. Memory of mice was detected by dark avoidance behavior in the 53" d and the 60"' d. Animals were sacrificed after the memory test; brain tissues were processed for Fos-ir and TH-ir by immunohistochemistry. Mice were divided into four groups according results of expri-ment 1, they received i.p. injection of apomorphine (0.1 mg/kg, APO 0.1, 0.5 mg/kg, APO 0.5, and 2.0 mg/kg, APO2.0 respectively, n = 10).
RESULTSMemory was inhibited in mice injected scopolamine 3.0 mg/kg. Latency was significantly less than in NS group, only 1/ 4 that of NS group (P > 0.05). The number of mistake of SCOP 3.0 group increased about four times than that of NS group (P > 0.05). But there was no difference of latency and number of mistake between SCOP 0.3 and NS group in expriment 1. Scopolamine-induced memory deficit was associated with decreased cellular activation, indicated by Fos immunoreactive (ir) staining, in NAcc CA1 and CA3 (P < 0.05), and also associated with decreases in the number of cells labeled for tyrosine hydroxylase (TH-ir), the rate limiting enzyme for dopamine conversion (P < 0.01) and the number of cells co-labeled for TH-ir/Fos-ir (P <0.01) in the ventral tegmental area(VTA), apomorphine lessened scopolamine-induced memory deficit in experiment 2. The number of cells co-labeled for TH-ir/Fos-ir (P <, 0.05) was increased in VTA after apomorphine treatment.
CONCLUSIONApomorphine lessened scopolamine-induced memory deficit in mice by increasing DA activities in VTA.
Animals ; Apomorphine ; pharmacology ; Disease Models, Animal ; Dopamine Agonists ; pharmacology ; Male ; Memory Disorders ; chemically induced ; drug therapy ; Mice ; Scopolamine Hydrobromide ; toxicity
2.Total flavonoids of Drynariae Rhizoma regulates ER-p38 MAPK signaling pathway to improve scopolamine-induced learning and memory impairments in model mice.
De-Ping ZHAO ; Da-Long LI ; Yan-Hang ZHANG ; Yue CUI ; Hong-Dan XU ; Bo YANG ; Xia LEI ; Ning ZHANG
China Journal of Chinese Materia Medica 2021;46(22):5922-5929
This study intended to explore the effect and mechanism of total flavonoids of Drynariae Rhizoma in improving scopola-mine-induced learning and memory impairments in model mice. Ninety four-month-old Kunming(KM) mice were randomly divided into six groups. The ones in the model group and blank group were treated with intragastric administration of normal saline, while those in the medication groups separately received the total flavonoids of Drynariae Rhizoma, Kangnaoshuai Capsules, donepezil, as well as total flavonoids of Rhizoma Drynariae plus estrogen receptor(ER) blocker by gavage. The mouse model of learning and memory impairments was established via intraperitoneal injection of scopolamine. Following the measurement of mouse learning and memory abilities in Morris water maze test, the hippocampal ERβ expression was detected by immunohistochemistry, and the expression levels of ERβ and phosphorylated p38(p-p38) in the hippocampus and B-cell lymphoma 2(Bcl-2), Bcl-2-associated death promoter(Bad), and cysteinyl aspartate-specific protease-3(caspase-3) in the apoptotic system were assayed by Western blot. The contents of malondia-ldehyde(MDA), superoxide dismutase(SOD), and nitric oxide(NO) in the hippocampus were then determined using corresponding kits. Compared with the control group, the model group exhibited significantly prolonged incubation period, reduced frequency of cros-sing the platform, shortened residence time in the target quadrant, lowered ERβ, Bcl-2 and SOD activity in the hippocampus, and increased p-p38/p38, Bad, caspase-3, MDA, and NO. Compared with the model group, the total flavonoids of Rhizoma Drynariae increased the expression of ERβ and SOD in the hippocampus, down-regulated the expression of neuronal pro-apoptotic proteins, up-re-gulated the expression of anti-apoptotic proteins, and reduced p-p38/p38, MDA, and NO. The effects of total flavonoids of Drynariae Rhizoma on the above indexes were reversed by ER blocker. It has been proved that the total flavonoids of Drynariae Rhizoma obviously alleviate scopolamine-induced learning and memory impairments in mice, which may be achieved by regulating the neuronal apoptotic system and oxidative stress via the ER-p38 mitogen-activated protein kinase(ER-p38 MAPK) signaling pathway.
Animals
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Flavonoids
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Hippocampus
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Maze Learning
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Mice
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Polypodiaceae
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Receptors, Estrogen
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Scopolamine/toxicity*
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Signal Transduction
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p38 Mitogen-Activated Protein Kinases/genetics*
3.Effect of Kangshuai Yizhi Formula I on learning and memory dysfunction induced by scopolamine in mice.
Jia WEI ; Da-xiang LU ; Ren-bin QI ; Hua-dong WANG ; Xue-hua JIANG
Chinese journal of integrative medicine 2010;16(3):252-257
OBJECTIVETo evaluate the improvement of Kangshuai Yizhi Formula I ( I, KYF I) on: the learning and memory dysfunction in mice, and on the mechanism of the hippocampal cholinergic system and the nervous system of monoamine which are closely related to learning and memory function.
METHODSMice: in the low-, middle-, and high-dose KYF I groups were given low-, middle-, and high-dose KYF, respectively, by gastrogavage for 35 successive days. Animals in the control group and the model group were treated with distilled water. The acute learning and memory dysfunction model was established by injection of scopolamine from day 31, and Morris water maze was used to assess the behavior performance of scopolamine-induced model mice for five days. The activities of acetylcholinesterase (AChE), choline acetyl transferase (ChaT) and the content of monoamine neurotransmitters in hippocampus were measured. The activity of monoamine oxidase (MAO) in hippocampus and serum was also detected.
RESULTS(1) Compared with the control group, the: mean escape latency was shortened, and the frequency across the platform and the staying time at the platform area on the 5th day were decreased in the model group by Morris water maze test. The activities of AChE and MAO were increased, and the ChaT activity and monoamine neurotransmitter content were decreased as well. (2) The escape latency for 4 days in the low-, middle-, and high-dose KYF I groups was significantly shortened than that in the model group, with the shortest latency in the high-dose KYF I group (P<0.05, P<0.01). The frequency across the platform was significantly increased and the staying time at the platform was significantly prolonged in the middle- and high-dose KYF I groups (P<0.05, P<0.01). (3) As compared with the model group, the activity of ChaT and the content of monoamine neurotransmitters in the hippocampus were significantly increased, and the activities of AchE and MAO were significantly decreased in the hippocampus in the high-dose KYF I group (P<0.01).
CONCLUSIONSHigh-dose KYF I can significantly improve the learning and memory dysfunction: induced by scopolamine in mice. Its mechanism may be related to improving the central cholinergic system and regulating the hippocampal monoamine neurotransmitters.
Acetylcholinesterase ; metabolism ; Animals ; Behavior, Animal ; drug effects ; Choline O-Acetyltransferase ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hippocampus ; drug effects ; enzymology ; pathology ; Learning ; drug effects ; Male ; Memory Disorders ; blood ; drug therapy ; enzymology ; physiopathology ; Mice ; Monoamine Oxidase ; blood ; Neurotransmitter Agents ; metabolism ; Reaction Time ; Scopolamine Hydrobromide ; toxicity ; Time Factors
4.Effects of Yizhi Capsule on learning and memory disorder and beta-amyloid peptide induced neurotoxicity in rats.
Hang-yu WU ; Jiang-ping XU ; Lin LI ; Bai-hua ZHU
Chinese journal of integrative medicine 2006;12(2):137-141
OBJECTIVETo explore the effects of Yizhi Capsule (YZC) on learning and memory disorder and beta-amyloid peptide induced neurotoxicity in rats.
METHODSVarious doses of YZC were administered to Sprague-Dawley (SD) rats for 8 consecutive days, twice a day. On the 8th day of the experiment, scopolamine hydrobromide was intraperitoneally injected to every rat and Morris water maze test and shuttle dark avoidance test were carried out respectively to explore the changes of learning and memory capacities in the rats. Besides, after the cerebral cortical neurons of newborn SD rats aged within 3 days were cultured in vitro for 7 days, drug serum containing YZC was added to the cultured neurons before or after beta amyloid peptide(25 - 35) (Abeta(25 - 35)) intoxication to observe the protective effect of YZC on neurotoxicity by MTT assay and to determine the LDH content in the supernatant.
RESULTSCompared with those untreated with YZC, the rats having received YZC treatment got superiority in shorter time of platform seeking in Morris water maze test, as well as elongated latent period and less times of error in shuttle dark avoidance test. On the cultured neurons, YZC drug serum could effectively increase the survival rate of Abeta(25 - 35) intoxicated neurons and reduce the LDH contents in cultured supernatant.
CONCLUSIONYZC has an action of improving learning and memory disorder, and good protective effect on Abeta(25 - 35) induced neurotoxicity in SD rats.
Amyloid beta-Peptides ; toxicity ; Animals ; Avoidance Learning ; drug effects ; Cells, Cultured ; Cerebral Cortex ; cytology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; L-Lactate Dehydrogenase ; analysis ; Learning ; drug effects ; Male ; Maze Learning ; drug effects ; Memory Disorders ; drug therapy ; Neurons ; drug effects ; Rats ; Rats, Sprague-Dawley ; Scopolamine Hydrobromide ; pharmacology