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OBJECTIVE@#To observe the effects of Yizhi Tiaoshen (benefiting mental health and regulating the spirit) acupuncture on learning and memory function, and the expression of phosphorylated tubulin-associated unit (tau) protein in the hippocampus of Alzheimer's disease (AD) model rats, and explore the effect mechanism of this therapy on AD.@*METHODS@#A blank group and a sham-operation group were randomly selected from 60 male SD rats, 10 rats in each one. AD models were established in the rest 40 rats by the intraperitoneal injection of D-galactose and okadaic acid in the CA1 region of the bilateral hippocampus. Thirty successfully-replicated model rats were randomly divided into a model group, a western medication group and an acupuncture group, 10 rats in each one. In the acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Sishencong" (EX-HN 1), "Neiguan" (PC 6), "Shenmen" (HT 7), "Xuanzhong" (GB 39) and "Sanyinjiao" (SP 6); and the needles were retained for 10 min. Acupuncture was given once daily. One course of treatment was composed of 6 days, with the interval of 1 day; the completion of treatment included 4 courses. In the western medication group, donepezil hydrochloride solution (0.45 mg/kg) was administrated intragastrically, once daily; it took 7 days to accomplish one course of treatment and a completion of intervention was composed of 4 courses. Morris water maze (MWM) and novel object recognition test (NORT) were used to assess the learning and memory function of the rats. Using HE staining and Nissl staining, the morphological structure of the hippocampus was observed. With Western blot adopted, the protein expression of the tau, phosphorylated tau protein at Ser198 (p-tau Ser198), protein phosphatase 2A (PP2A) and glycogen synthase kinase-3β (GSK-3β) in the hippocampus was detected.@*RESULTS@#There were no statistical differences in all of the indexes between the sham-operation group and the blank group. Compared with the sham-operation group, in the model group, the MWM escape latency was prolonged (P<0.05), the crossing frequency and the quadrant stay time in original platform were shortened (P<0.05), and the NORT discrimination index (DI) was reduced (P<0.05); the hippocampal cell numbers were declined and the cells arranged irregularly, the hippocampal neuronal structure was abnormal and the numbers of Nissl bodies decreased; the protein expression of p-tau Ser198 and GSK-3βwas increased (P<0.05) and that of PP2A decreased (P<0.05). When compared with the model group, in the western medication group and the acupuncture group, the MWM escape latency was shortened (P<0.05), the crossing frequency and the quadrant stay time in original platform were increased (P<0.05), and DI got higher (P<0.05); the hippocampal cell numbers were elevated and the cells arranged regularly, the damage of hippocampal neuronal structure was attenuated and the numbers of Nissl bodies were increased; the protein expression of p-tau Ser198 and GSK-3β was reduced (P<0.05) and that of PP2A was increased (P<0.05). There were no statistically significant differences in the above indexes between the acupuncture group and the western medication group (P>0.05).@*CONCLUSION@#Acupuncture therapy of "benefiting mental health and regulating the spirit" could improve the learning and memory function and alleviate neuronal injure of AD model rats. The effect mechanism of this therapy may be related to the down-regulation of GSK-3β and the up-regulation of PP2A in the hippocampus, and then to inducing the inhibition of tau protein phosphorylation.
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Male , Animals , Rats , Rats, Sprague-Dawley , Glycogen Synthase Kinase 3 beta , Tubulin , Alzheimer Disease/therapy , tau Proteins/genetics , Acupuncture Therapy , HippocampusABSTRACT
Objective To explore the protective effect and mechanism of swimming rehabilitation training on learning and memory impairment of cerebral ischemia reperfusion gerbil. Methods Forty adult healthy male gerbils were randomly divided into sham group,sham+swimming group (Sham+S group),cere-bral ischemia / reperfusion group ( I/R group), cerebral ischemia/reperfusion+swimming group ( I/R+S group),with 10 rats in each group. The gerbil models of cerebral ischemia/reperfusion in I/R group and I/R+S group were established by blocking bilateral common carotid artery,while for gerbils in Sham group and Sham+S group, only bilateral common carotid arteries of gerbils were exposed, but no arteries were clamped. Morris water maze was used to detect the changes of learning and memory function in rats. Oxida- tive stress injury in hippocampal neurons was detected by detection kit analysis. And the expression of Bax, Bcl-2 and CaMK Ⅱ protein in hippocampal tissue was detected by Western blot. Results Compared with Sham group,the gerbils in I/R group had longer positioning cruise time and less shuttle times ( both P<0. 01). Compared with I/R group,the positioning cruise time and shuttle times in I/R+S group were signifi-cantly shortened and increased respectively (both P<0. 01). Compared with sham group( SOD:(123. 13± 7. 50)U/mg,GSH:(42. 10±2. 17) μg/g,GSH-Px:(61. 37±2. 51) μg/g,MDA:( 2. 91± 0. 23) nmol/mg), the activities of SOD,GSH,GSH-Px in I/R group decreased significantly,while the content of MDA increased significantly(SOD:(75. 50±6. 96)U/mg,GSH:(22. 50±1. 64) μg/g,GSH-Px:(33. 15±2. 04)μg/g,MDA:(5. 96±0. 32)nmol/mg;all P<0. 01). Furthermore,compared with I/R group,the above indexes in I/R+S group were significantly reversed(SOD:(110. 30±5. 90)U/mg,GSH:(34. 31±1. 73)μg/g,GSH-Px:(50. 13 ±2. 31)μg/g,MDA:(3. 57±0. 29) nmol/mg;all P<0. 01). Compared with Sham group,the expression of Bax protein in hippocampus of gerbils in I/R group was increased,while the expression of Bcl-2 protein and p-CaMK Ⅱ protein was decreased (all P<0. 05). Compared with I/R group,the expression of Bax protein in hippocampus of gerbils in I/R+S group was decreased,while the expression of Bcl-2 protein and p-CaMK Ⅱprotein was increased (all P<0. 05). Conclusion Swimming rehabilitation training can improve learning and memory impairment of gerbils after ischemia-reperfusion through anti-oxidative stress and anti-apoptosis, which may be related to CaMK Ⅱ signaling system.
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Objective • To investigate the role of group I metabotropic glutamate receptor (mGluR) in the regulation of N-methyl-D-aspartic acid receptor (NMDAR)-mediated synaptic plasticity in low dose ketamine protecting learning and memory function after modified electroconvulsive shock (MECS). Methods • The 2-3-month-old Sprague Dawley (SD) rats were used to establish depression models with chronic unpredictable mild stress. Ten healthy rats were used as the control group (group C), and another 30 depressed rats were randomly divided into group D, group M, and group KM. Group C was not treated, group D was treated with pseudo-MECS after intraperitoneal injection of normal saline, group M was given intraperitoneal injection of propofol, and group KM was given intraperitoneal injection of propofol combined with low-dose ketamine (10 mg/kg). Both group M and group KM underwent MECS. The sucrose preference test was used to evaluate the depression status. The Morris water maze was used to detect the spatial learning and memory function. The expression of NMDAR1, mGluR1 and mGluR5 proteins in the hippocampus was detected by Western blotting. Another 36 depressed rats were randomly divided into 6 groups: group DE, group m1E, group m5E, group DE', group m1E', and group m5E'. Group DE and group DE' were perfused with artificial cerebrospinal fluid alone. Group m1E and group m1E' were perfused with artificial cerebrospinal fluid containing mGluR1 blocker. Group m5E and group m5E' were perfused with artificial cerebrospinal fluid containing mGluR5 blocker. Long-term potentiations (LTP) were detected in group DE, group m1E, and group m5E. NMDAR-mediated field potentials (fEPSPNMDAR) were detected in group DE', group m1E', and group m5E'. Results • After treatment, the sucrose preference percentages of group M and group KM increased compared with group D (P<0.05), the escape latencies (EL) of group M and group KM were prolonged (P<0.05), and the space exploration times (SET) were shortened (P<0.05). Compared with group M, the EL of group KM was shortened (P<0.05), and the SET was prolonged (P<0.05). Compared with group D, the expression levels of NMDAR1, mGluR1 and mGluR5 in group M and group KM decreased (P<0.05). Compared with group M, the expression levels of NMDAR1, mGluR1 and mGluR5 in group KM increased (P<0.05). Compared with group DE, the LTP decreased in group m1E and group m5E (P<0.05). Compared with group DE', the fEPSPNMDAR of group m1E' and group m5E' decreased (P<0.05). Conclusion • Ketamine up-regulates NMDAR1 and group mGluR expression to enhance the activation of NMDAR in the hippocampus which may be responsible for the protective effects on spatial learning and memory function in depression rats undergoing MECS.
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Objective To explore the effects of Guilingji on improving learning and memory dysfunction caused by aging. Methods The mouse model of subacute aging caused by D-galactose and the rat model of natural aging were used respectively to imitate learning and memory dysfunction caused by aging. The effects of Guilingji on improving of learning and memory function index were focused in the diving platform experiment and the Morris water maze experiment. At the same time, the effect of that on rat organ index and blood biochemical index were investigated. Results Guilingji can significantly prolong step down latency (P < 0.05) and reduce the number of errors within 5 min (P < 0.05, 0.01) of the model mice. It can shorten positioning navigation escape incubation period (P < 0.01), extend the space exploration quadrant retention time (P < 0.05, 0.01), and increase the number of access to the platform (P < 0.05). Guilingji can increase testicular, thymus and spleen index (P < 0.05) and reduce the ALT content in serum (P < 0.05). Conclusion Guilingji can obviously improve the impairment of learning and memory function caused by aging. It also has some good effects on enhancing immunity, improving reproductive capacity, and protecting liver.
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Objective:To explore the effect of sevoflurane on learning and memory function and apoptosis of hippocampus in infant rats. Methods:100 SD rats aged 6-8 days were randomly divided into 5 groups(n=20),the group Ⅰinhaled 3% sevoflurane and 25% oxygen for 2 hours;the groupⅡinhaled only 25% oxygen for 2 hours;the groupⅢinhaled 3% sevoflurane and 25% oxygen for 2 hours on the 6th,7th,8th day after birth;the group Ⅳ inhaled 25% oxygen for 2 hours on the 6th,7th,8th day after birth;groupⅤ were just put into the anesthetized box without any treatment. When the rats were grown up to 16-21 days after anesthesia,the effect of learning and memory function were assessed by Morris water maze test,and activity of caspase-3 were detected by Western blot,the apoptosis of hippocampus were detected by tunnel. Results:①Compared to groupⅣ,the mean escape lantency of groupⅠshowed no significant changes(P>0. 05),while group Ⅲ was significant longer (P<0. 05),which was significant different from other groups(P<0. 05).②In the space exploration experiment,there was no difference between group Ⅰ and Ⅳ,but compared to group Ⅰ and other groups,the number of cross platform of groupⅢwas decreased (P<0. 05).③The swimming speed of groupⅢwas significantly slower than the other groups.④Compared to group Ⅳ,the activity of caspase-3 slightly increased in group Ⅰ,and significantly increased in group Ⅲ( P<0. 05 ) . ⑤The positive cells in hippocampus stained by TUNEL in group Ⅲ was significant increased ( P<0. 05 ) . Conclusion:Learning and memory function of infant rats aged 6-8 days are impaired after three exposures to sevoflurane when they grow up to 16-21 days,and this may relate to the apoptosis of hippocampus.
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Objective·To investigate the effect of mesenchymal stem cells (MSCs) on autophagy in hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods·Western blotting was used to detect the expression levels of autophagy associated proteins Beclin1, LC3 Ⅱ , and p62 in the hippocampus of HIBD rats following MSCs transplantation and oxygen glucose deprivation (OGD)-injured primary neurons following MSCs seperated coculture. The learning-memory function in the HIBD rats after MSCs transplantation was tested by Morris water maze test. Transmission electron microscopy was also used to observe the number of autophagic neurons in OGD damaged neurons after coculture with MSCs. Results·The levels of Beclin1 and LC3 Ⅱ protein expressions were significantly increased at 12-24 h in the rat hippocampus following HIBD injury. MSCs transplantation statistically downregulated the autophagy level in the hippocampus, and obviously improved the learning-memory function of HIBD rats. Meanwhile, the levels of Beclin1 and LC3 Ⅱ protein expressions in the primary neurons in vitro were also induced by OGD for 12 h. MSCs seperated coculture significantly downregulated the autophagy level of hippocampal neurons by OGD injury, decreased the number of autophagosome in the OGD-injured neurons. Conclusion·MSCs may inhibit the autophagy of hippocampal neurons by partly regulating the damaged microenvironment to improve the learning and memory function of HIBD rats.
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To review the research progress in the chemical constituents from the husks of Xanthoceras sorbifolia and their biological activities for the first time. After a detailed investigation on the literatures at home and abroad, we had found that the primary chemical constituents from the husks of X. sorbifolia were triterpenoids and polyphenols (such as flavonoids, phenolic acids, coumarins etc), sterols, alkaloids, and so on. The biological activities of the chemical constituents from the husks of X. sorbifolia showed mainly as improving the ability of learning and memory, anticancer effects, inhibition on tyrosinase, curing cardiovascular and cerebrovascular diseases, anti-oxidant and anti-inflammatory effects, and inhibiting pancreatic lipase activity. Xanthoceraside is a primary triterpenoid saponin purified from the husks of X. sorbifolia, with highest content and a variety of biological activities. The husks as the waste of the oil-extracting from X. sorbifolia, this paper provides the references for further understanding and utilization of the medicinal values in the husks of X. sorbifolia.
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@#ObjectiveTo investigate effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), on learning and memory function and excitability in Alzheimer's disease rat model induced by cholinergic damage.MethodsBasal forebrain of rats were injured by ibotenic acid injection of 10μg each side. Rats were divided into six groups as the operation, model, positive control drug donepezil hydrochloride, TSG low (0.03g/kg), middle (0.06g/kg) and high (0.12g/kg) dose groups. These drugs were intragastrically administrated for 1 month. The learning and memory function were determined with Morris water maze, channel water maze and step through tests, and the excitability was evaluated by open field analysis. Results TSG (low, middle and high dose)significantly decreased the swimming time and error times (P<0.05) in water maze test and TSG high dose improved the ability of passive avoidance response at step through test.Open field test showed that there was no significant difference on excitability between each group ConclusionTSG can improve learning and memory abilities of Alzheimer's disease rat induced by cholinergic damage, TSG(low and middle dose)improve excitability of central nervous system in Alzheimer's disease rat model,but TSG dose maybe inhibite excitability of central nervous system.
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Objective To study on FBD (composed with Poria cocos, Atractylodes macrocephala, and Angelica sinensis) used to improve learning and memory function of animals. Methods The mice were treated by ig FBD with the doses of 35, 70 and 140 mg/kg for one week continuously. Effect of FBD on dysmnesia of acquired learning of mice induced by scopolamine, dysmnesia of memory retention of mice induced by NaNO2, and dysmnesia of reappearance of memory of mice induced by 45% ethanol were studied. Improvement for the dysmnesia of memory due to chronic blood deficiency in brain of rats induced by ligating the carotid arteries of two sides were observed. Results FBD can improve the dysmnesia of mice induced by scopolamine, NaNO2, and 45% ethanol significantly, also dysmnesia due to chronic blood deficiency in brain of rats induced by ligating the carotid arteries. Conclusion FBD has the function to improve the learning and memory function of animals.
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Object To observe the improving effects of BUSHEN YIZHI DECOCTION (BSYZD) on interspace explore learning and memory in rat model with Alzheimer's disease. Methods Eighty 15-month Wistar rats were induced by ip D -galactose for four weeks and injection of basal nucleus of Meynert with ibotenic acid (IBO) to make AD model, then randomly divided into AD model group, Hup-A treated group, BSYZD (high dose, 12 g/kg?d) treated group and BSYZD (low dose, 6 g/kg?d) treated group, and also normal aged and young groups. After treating for four weeks, Morris water maze was used to assess the improvement of rat interspace explore learning and memory. Results In the interspace explore experiment, the significant differences were observed between the model, Hup-A treated groups and normal aged, young groups (P0.05). Conclusion BSYZD possesses a certain preventive effects on interspace explore learning and memory in AD rat model.
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Repeated administrations of gangliosides extracted from Cervus nippon Temminek exerted remarkable facilitation action on the acquisition, retrieval and consolidation of memory in mice. It was able to increase the incorporations of [8H] Leucine into protein and [3H] Uridine into RNA in mouse brain tissue. It was suggested that the above-mentioned actions of gangliosides may be due to the promoting action for the synthesis of protein in brain tissue.