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OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with Gastrodin on learning-memory ability and expression of silent information regulator 2 homologous protein 1(SIRT 1) and peroxisome proliferator activated receptor γ coactivator (PGC-1 ɑ) of hippocampal CA 1 region in Alzheimer's disease(AD) rats, so as to explore its mechanism under-lying improvement of AD. METHODS: Sixty male SD rats were randomly divided into normal control (normal), sham operation (sham), model, EA, Gastrodin and EA＋ Gastrodin groups (n＝10 in each). The AD model was established by intraperitoneal injection of D-Galactose (120 mg•kg－1•d－1) combined with bilateral hippocampal injection of β amyloid 1-40(Aβ 1-40). EA was applied at "Baihui"(GV 20), "Dazhui"(GV 14) and "Zusanli"(ST 36) for 30 min, once daily for 4 weeks. For rats of the Gastro-din group and EA＋ Gastrodin group, intraperitoneal injection of gastrodin(10 mg/kg) was conducted once daily for 4 weeks. Morris water maze tests were used to assess the rat's learning-memory ability. Nissl staining was used to assess the morphological changes of neurons in the hippocampal CA 1 area. The expression of SIRT 1 and PGC-1 ɑ of hippocampal CA 1 region was mea-sured by immunohistochemical staining. RESULTS: 1) Morris water maze tests showed that, compared with the normal and sham group, the escape latency was significantly prolonged (P<0.05), and the percentage of platform quadrant residence duration and the platform crossing times were considerably decreased in the model group (P<0.05). After the intervention, the escape latency was obviously shortened (P<0.05), and the percentage of platform quadrant residence duration and the platform crossing times were markedly increased in the EA, Gastrodin and EA＋Gastrodin groups relevant to the model group (P<0.05). 2) Nissl staining showed that, in comparison with the normal group or sham group, the number of cells in the hippocampal CA 1 area was decreased and the arrangement was disorganized in the model group. The number of cells in CA 1 area was relatively higher in the 3 treatment groups than in the model group. 3) The expression levels of SIRT 1 and PGC-1 ɑ proteins in the hippocampal CA 1 area were significantly down-regulated in the model group than in the normal and sham groups (P<0.05). After the intervention, the expression levels of SIRT 1 and PGC-1 ɑ in the EA, Gastrodin and EA＋Gastrodin groups were significantly up-regulated compared with the model group (P<0.05). The effects of EA＋Gastrodin were significantly superior to those of simple EA and simple Gastrodin in shortening the escape latency, up-regulating the expression levels of SIRT 1 and PGC-1 ɑ as well as in increasing the percentage of platform quadrant residence time and platform crossing times (P<0.05). CONCLUSION: Both EA and Gastrodin can improve the learning-memory ability of AD rats, which may be related to their effects in up-regulating the expression of SIRT 1 and PGC-1 ɑ and reducing neuronal injury in the CA 1 region of hippocampus, suggesting a protective role of EA on hippocampal neurons. The effect of EA combined with Gastrodin is markedly better than that of EA and Gastrodin alone.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) on changes of learning-memory ability, psychomotor coordination and anxiety-like behavior of cerebral hypoxic-ischemia (CHI) young rats, so as to explore its protective effect on neurons under hypoxic-ischemic conditions. METHODS: SD rats (aged 7 days) were randomly divided into sham operation (sham, n=12), model (n=11), and EA groups (n=12). In addition, 6 young rats in each group were used for observing the number of dendritic spines after Golgi staining. The CHI model was established by ligation of the left common carotid artery combined with hypoxia in a closed transparent vessel. EA was applied to "Baihui" (GV 20)and "Dazhui" (GV 14) for 20 min, once every other day, for 28 days. The rats' behavior changes were assessed by using rotarod performance (for psychomotor coordination), elevated plus maze (anxiety-like behavior) tests and Morris water maze (learning-memory ability) tests, separately. RESULTS: After modeling, the average escape latency and average escape distance of location navigation test within 70 seconds were significantly increased (P0.05). The density of dendritic spines was significantly lo-wer in the model group than in the sham group (P <0.05), and notably higher in the EA group than in the model group (P<0.05). CONCLUSION: EA can improve the learning-memory ability of CHI young rats, which may be related to its effect in protecting the dendritic spines of CA 1 region of hippocampus from injury.
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Objective To investigate the effects of Abnormal Phlegmatic Munziq on ability of learning and memory, and protein expressions of brain tissue RAGE and LRP1 of APP/PS1 transgenetic mice model of AD;To discuss its mechanism of action. Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups: model control group, positive control group, Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups, 18 mice in each group. Another 18 three-month-old C57BL/6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in ability of learning and memory of mice were detected by Step-down test; protein expressions of LRP1 and RAGE were detected by immunohistochemistry and Western blot. Results Compared with the normal control group, the reaction time of learning grades and the mistake times increased, incubation of memory grades decreased and the mistake times increased in the model control group (P<0.01);Compared with the model control group, the reaction time of learning grades and the mistake times decreased, incubation of memory grades increased and the mistake times decreased in all administration groups (P<0.05, P<0.01). Immunohistochemistry and Western blot results showed that compared with normal control group, the LRP1 expression decreased and RAGE increased in the model control group (P<0.05);Compared with the model control group, the LRP1 expression decreased and RAGE increased in Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups (P<0.05,P<0.01). Conclusion Abnormal Phlegmatic Munziq can improve ability of spatial learning and memory in APP/PS1 mice and regulate the expressions of RAGE and LRP1.
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Objective To investigate the intervention effects ofYinao Jieyu Prescription on the behaviors and damages in hippocampal CA1 area of the rats with post-stroke depression (PSD).Methods Totally 168 SPF male SD rats were randomly divided into normal group, sham-operation group, stroke group, PSD group, Western medicine group and TCM group. There were 24 rats in the normal group and sham-operation group, and 30 rats in the other groups. Rats in the normal group received no intervention. Rats in the sham-operation group received no suture. Rats in the stroke group were given middle cerebral artery occlusion operation and normally fed after operation. Rats in the PSD group, Western medicinal group and TCM group were made into PSD models by chronic immobilization stress for one week and individual battery to the end. At the inception of modeling, Western medicine group received fluoxetine hydrochloride for gavage; TCM group receivedYinao Jieyu Prescription for gavage; other groups received distilled water for gavage, once a day. At the end of week 2, 4, and 8, the morphology of the hippocampal CA1 area in each rat was observed by microscope after HE stained.Results Except for the week 2, at the same time point, the behavior scores of the rats in the TCM group were higher than those in the PSD group. At the same time point, the CA1 region of the hippocampus in the TCM group was more complete than the PSD group, and the cells were arranged neatly and in normal morphology.ConclusionYinao JieyuPrescription can improve the symptoms of PSD rats, and has protective effects on hippocampal CA1 area.
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Mammalian target of rapamycin (mTOR) has an important role in various biological processes in cells. In the present study, we investigated temporal changes in mTOR and phosphorylated-mTOR (p-mTOR) expressions in the rat hippocampal CA1 region following chronic cerebral hypoperfusion (CCH) induced by permanent bilateral common carotid arteries occlusion (2VO). The mTOR immunoreactivity in the pyramidal neurons and mTOR protein level in the hippocampal CA1 region were markedly decreased at 21 and 28 days after 2VO surgery. However, p-mTOR protein expression was significantly increased at 7 days following CCH but then decreased with time. The results indicate that mTOR and p-mTOR expressions change in the hippocampal CA1 region after 2VO surgery and that reduced expressions of mTOR and p-mTOR may be closely related to the CCH-induced neuronal damage in the hippocampal CA1 region.
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Animals , Rats , Biological Phenomena , CA1 Region, Hippocampal , Carotid Artery, Common , Dementia, Vascular , Mammals , Neurons , Pyramidal Cells , Sirolimus , TOR Serine-Threonine KinasesABSTRACT
Background: In Nepali and Indian system of traditional medicine, Withania somnifera (WS) is considered as a rejuvenative medicine to maintain physical and mental health and has also been shown to improve memory consolidation. Objective: In this study, a methanolic extract of WS (mWS) was applied on mice hippocampal CA1 neurons to identify the receptors activated by the WS. Materials and Methods: The whole cell patch clamp recordings were performed on CA1 pyramidal neurons from immature mice (7‑20 postnatal days). The cells were voltage clamped at ‑ 60 mV. Extract of WS root were applied to identify the effect of mWS. Results: The application of mWS (400 ng/μl) induced remarkable inward currents (‑158.1 ± 28.08 pA, n = 26) on the CA1 pyramidal neurons. These inward currents were not only reproducible but also concentration dependent. mWS‑induced inward currents remained persistent in the presence of amino acid receptor blocking cocktail (AARBC) containing blockers for the ionotropic glutamate receptors, glycine receptors and voltage‑gated Na+ channel (Control: ‑ 200.3 ± 55.42 pA, AARBC: ‑ 151.5 ± 40.58 pA, P > 0.05) suggesting that most of the responses by mWS are postsynaptic events. Interestingly, these inward currents were almost completely blocked by broad GABAA receptor antagonist, bicuculline‑ 20 μM (BIC) (BIC: ‑1.46 ± 1.4 pA, P < 0.001), but only partially by synaptic GABAA receptor blocker gabazine (1 μM) (GBZ: ‑18.26 ± 4.70 pA, P < 0.01). Conclusion: These results suggest that WS acts on synaptic/extrasynaptic GABAA receptors and may play an important role in the process of memory and neuroprotection via activation of synaptic and extrasynaptic GABAA receptors.
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Objective To explore the neuroprotective role of Genistein (GEN) on hippocampal CA1 neurons and the possible mechanism following global cerebral ischemia ( GCI) in rats.Methods Seventy five rats were subjected to global cerebral ischemia ( GCI ) by four-vessel occlusion and randomly divided into five groups , sham, ischemia/reperfusion (I/R), GEN, ICI 182,780 and vehicle groups.Fluoro-Jade B and neuron-specific nuclear-binding protein ( NeuN) staining was used to observe CA 1 neuronal survival .TUNEL was used to detect apoptotic neurons .Spatial learning and memory function of the rats were evaluated by Morris water maze .Results The best dose of neuroprotective role of GEN was 1.0mg/kg body weight.Compared with sham, TUNEL-positive neurons in the hippocampal CA1 region increased significantly in I/R and vehicle groups (P<0.01), while post-treatment with GEN (1.0mg/kg) at 5min after ischemia by tail vein injection decreased markedly (P<0.01).Treatment of 1.0mg/kg GEN markedly attenuated spatial learning and memory deficits of the rats after ischemic insult compared to I /R group.Furthermore, ICI 182,780 significantly abolished the neuroprotective role of GEN (P <0.01).Conclusion The low-dose (1.0mg/kg) GEN significantly attenuates neuronal damage and cognitive deficits following GCI in rats , and the mechanism may be involved in estrogen receptor activity.
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Aim To examine subcellular localization of serotonin 5-HT2A receptor (5-HT2AR) and glutamate NMDA receptor in dorsal hippocampal CA1 area ( dCA1 ) and further explore the effect of systemic acti-vation of 5-HT2A R on hippocampal neuronal firing rate. Methods The distribution of 5-HT2A R and NMDA re-ceptor in the dCA1 region was detected with immune e-lectron microscopy after embedding. The effect of acti-vation of 5-HT2A R on the principal neuron and inter-neuron firing rates was examined with multichannel re-cording. Results 5-HT2A R immunoreactivity was ob-served in the dCA1 neurons, including rough endoplas-mic reticula and mitochondria, and the 5-HT2A R and glutamate NMDA receptors were colocalized in the syn-aptic membrane, vesicle and neurofilament of the hipp-ocampal neuron. 5-HT2A R activation increased princi-pal neuronal firing rate and the interneuronal firing rate was not changed. Conclusion The 5-HT2A R and NM-DA receptor are colocalized in dCA1 neurons, and acti-vation of 5-HT2A R increases hippocampal principal neuronal firing rate.
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OBJECTIVE: To study the activity of TQHXD on the learning and memory ability of rats with vascular dementia(VD) and its effects on the content of Ach in cerebral cortex. And to investigate the action mechanism of TQHXD on VD in rats. METHODS: VD model was made by common carotid artery injection of a co-thrombus inducer. The 8-arm radial maze experiment was adopted to evaluate the times of working memory errors and reference memory errors. The changes of the pathological area in hippocampus CA1 were observed by optical microscope. Enzyme-linked immunosorbent assay was used to determine the concentration of Ach in rats cerebral cortex. RESULTS: High and middle dose of TQXHD significantly reduce the times of working memory errors and reference memory errors (P<0.01), definitely improved the anormalies of pathological area in hippocampal CA1, and significantly increased the content of Ach in cerebral cortex (P<0.01). CONCLUSION: TQHXD can significantly ameliorate the learning and memory ability of in VD rats. The mechanism may be related to the improvement of the vertebral body cells anomalies in the hippocampal CA1 region and increasing the content of the Ach in cerebral cortex. Copyright 2012 by the Chinese Pharmaceutical Association.
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Objective To analyse the variability of spontaneous firing frequencies and firing patterns of a Hippocampal CA1 neuron with the changes of extracellular potassium concentration[K+]0 and ion channel conductance.Methods A 16-compartment cable model of a Hippocampal CA1 neuron was developed based on the Warman model with computer software MATLAB.The dendrites contained no active channels,while five active channels (INa,INap,IDR,IA,IM)were contained in soma.In the model,the calcium currents and potassium currents(ICm,,ICT and IAHP) regulated by calcium concentration were not included.ResultsSimulation results showed that the neuron could generate periodicspontaneous firing activity.The spiking frequency increased with the increasing of[K+]0 and sodium conductance and decreasing of potassium conductance.Spontaneous single neuron activity appeared in singlet or in grouped bursts of two or three spikes.Conclusion The variability of spontaneous firing frequencies and firing patterns of single neuron are relevant to[K+]0 and ion channel conductance.
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Objective To observe the effect of electroacupuncture (EA) plus oxygenmedicine (OM) on the expression of Bcl-2 and Bax in the hippocampal CA 1 area in cerebral ischemia/reperfusion injury (CI/RI) rats. Methods Thirty SD rats were randomized into sham-operation,model,EA,OM,EA+OM groups (n=6/group). CI/RI model was established by using modified Pulsinelli 4 vessel occlusion and reperfusion. EA (100 Hz,3.5 mA) was applied to "Baihui" (GV 20) and "Zusanli" (ST 36) 30 min,once daily for 4 days. Rats of OM and EA+OM groups were put into a box filled with oxygen and atomized herbal medicines containing Bingpian (Borneolum),Shexiang (Moschus),Huangjing (Rhizoma Polygonati),Shouwu (Radix Polygoni Multiflori),etc. for 30 min,once daily for 4 days. Bcl-2 and Bax expression of the hippocampal CA 1 area was detected by immunohistochemistry. Results Compared with sham group,the numbers of Bcl-2 immunoreaction (IR) and Bax IR positive cells,and the immunoactivity of Bcl-2 IR and Bax IR positive products in the hippocampal CA 1 area were increased significantly in model group (P0.05). Conclusion EA and OM and EA+OM can effectively regulate the expression of Bcl-2 and Bax in the hippocampal CA 1 area in CI/RI rats,and the effects of EA+OM are significantly superior to those of simple EA and simple OM,which may contribute to their effect in improving cerebral ischemia.
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Changes of single unit activity of CA1 hippocampus region were investigated in anesthetized Mongolian gerbils for six days following transient ischemia. Ischemia was produced immediately before the implantation of micro-wire recording electrodes. In control animals receiving pseudo-ischemic surgery, neither spontaneous neuronal activities (5.70+/-0.4 Hz) nor the number of recorded neurons per animal changed significantly for six days. Correlative firings among simultaneously recorded neurons were weak (correlation coefficient >0.6) in the control animals. Animals subjected to ischemia exhibited a significant elevation of neural firing at post-ischemic 12 hr (9.95+/-0.9 Hz) and day 1 (8.48+/-0.8 Hz), but a significant depression of activity at post-ischemic day 6 (1.84+/-0.3 Hz) when compared to the activities of non-ischemic control animal. Ischemia significantly (correlation coefficient <0.6) increased correlative firings among simultaneously recorded neurons, which were prominent especially during post-ischemic days 1, 2 and 6. Although the numbers of spontaneously active neurons recorded from control group varied within normal range during the experimental period, those from ischemic group changed in post-ischemic time-dependent manner. Temporal changes of the number of cells recorded per animal between control group and ischemic group were also significantly different (p = 0.0084, t = 3.271, df = 10). Cresyl violet staining indicated significant loss of CA1 cells at post-ischemic day 7. Overall, we showed post-ischemic time-dependent, differential changes of three characteristics, including spontaneous activity, network relationship and excitability of CA1 cells, suggesting sustained neural functions. Thus, histological observation of CA1 cell death till post-ischemic day 7 may not represent actual neuronal death.
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Animals , Cell Death , Depression , Electrodes , Fires , Gerbillinae , Hippocampus , Ischemia , Neurons , Reference Values , ViolaABSTRACT
Objective To study the effect of intracerebroventricular(icv) injectionon acetylcholine(ACh) on the elecric activities of pain-related neurons in the hippocampal CA1 area of rat.Methods Trains of the electric impulses applied to the right sciatic nerve were used as noxious stimuli.The discharges of neurons were led out by extracellular recording method with glass microelectrodes.Results Icv injection of ACh(20?g/10?l) caused an decrease of the evoked discharge frequency of pain-excited neurons(PEN) and a prolongation latency as well as an increase of the evoked discharge of pain-inhibited neurons(PIN) and a shortening of inhibitory duration.Conclusion The response of pain-related neurons in hippocampal CA1 area to the noxious stimulation is weakened by icv injection of ACh,exhibiting analgesic effect.
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Objective To investigate the effects of Panax notoginseng saponins(PNS)on both the excitatory and inhibitory synaptic transmission in the pyramidal neurons in hippocampal CA1 region of rats.Methods Wistar male rats(3—4 weeks)were killed by cervical dislocation and hippocampal slices(400 ?m)were prepared,blind whole-cell voltage-clamp recordings were performed on the CA1 pyramidal cells in hippocampal slices to examine and analyze the effects of PNS(0.05—0.4 g/L)on CA1 afferent fiber-evoked excitatory postsynaptic currents(EPSCs)and inhibitory postsynaptic currents(IPSCs),respectively.Moreover,the Schaffer collateral/commissural pathway was stimulated with paired pulses(interpulse interval was 50 ms)and the paired-pulse facilitation(PPF)was analyzed by EPSC2/EPSC1(P2/P1)ratio.Results PNS(0.1—0.4 g/L)significantly depressed amplitude of EPSCs in neurons in the hippocampal CA1 region(P0.05).Conclusion The inhibitory effect of PNS on EPSCs in hippocampal CA1 pyramidal neurons is not due to the reinforcement of the inhibiting interneurons.It may be a result of direct inhibition on excitatory synaptic transmission.The increasing of P2/P1 ratio after PNS application suggests that PNS depresses the excitatory synaptic transmission by presynaptic mechanism.
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0.05). After experimental cerebral hemorrhage for 4 hours of model group, blood pressure and P O 2 were obvious increased( P 0.05), but they were lower than model group at the meantime ( P
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Objective To explore the effect of androgen on learning and memory ability and neurons in hippocampal CA1 region in senescence accelerated mouse prone strain/8(SAMP8).Methods Thirty 7-month-old male SAMP8 were randomly divided into sham-operation control group,castrated group and androgen replacement therapy after castration group.The dose of testosterone undecanoate(TU) was 37.4mg/(kg?15d).The capability of learning and memory was observed 45 days later through the Morris water maze(MWM) test and the change of neurons in hippocampal CA1 region was detected and analyzed by HE staining,immunohistochemal method and computer pathological image analysis system.Results 1.In the MWM test,the escape latency of castrated group were significantly prolonged(P0.05).2.With HE staining,neurons in hippocampal CA1 region of castrated group were found with diffused vacuolar degeneration,and sparse and disordered cellular arranpement.The cell nucleuses were karyochrome and karyopycnosis.The number and optical density of A? immune positive neurons were markedly higher than those of other groups(P