Concentraciones de oxígeno intermitentes tienen impacto en el desarrollo postnatal temprano de ratas Sprague-Dawley: efectos en CA1 del hipocampo / Intermittent oxygen concentrations have an impact on the early postnatal development of Sprague-Dawley rats: effects on hippocampal CA1

El periodo postnatal temprano se caracteriza por rápido crecimiento cerebral, posiblemente relacionado con variaciones del oxígeno tisular. Esto ha motivado el estudio de protocolos que suministran diferentes concentraciones de oxígeno intermitentes, para observar sus efectos morfológicos y cerebrales. Se utilizaron 52 crías de ratas Sprague Dawley, distribuidas en igual número a cuatro grupos experimentales, Control (C, 21 %O2), Hipoxia Intermitente (HI, 11 %O2), Hiperoxia Intermitente (HOI, 30 %O2) e Hipoxia Hiperoxia Intermitente (HHI, 11 % -30 %O2). Los protocolos consideraron 5 ciclos de 5 minutos de dosificación, durante 50 minutos diarios. Se realizó en una cámara semihermética entre los días 5 al 11 postnatales. Las evaluaciones de crecimiento corporal y cuantificación neuronal, se realizaron en las crías macho, en el día 28 postnatal. El peso corporal en el grupo hipoxia intermitente mostró diferencias significativas respecto al grupo hiperoxia intermitente (HI vs HOI, p<0,01) y al grupo hipoxia-hiperoxia Intermitente (HI vs HHI, p< 0,001). La talla corporal disminuyó en el grupo hipoxia-hiperoxia intermitente con diferencias significativas respecto del grupo control (C vs HHI, p<0,05) y respecto del grupo hipoxia intermitente (HHI vs HI, p< 0,01). El conteo neuronal en el área CA1 del hipocampo aumentó en el grupo hipoxia intermitente con diferencias significativas respecto a los grupos control (C vs HI; p<0,05), al grupo hiperoxia intermitente (HI vs HOI; p<0,001) y al grupo hipoxia-hiperoxia intermitente (HI vs HHI; p<0,001). Finalmente, el grupo hipoxia- hiperoxia Intermitente disminuyó significativamente en la cantidad de neuronas en comparación al grupo hiperoxia intermitente (HHI vs HOI; p<0,001). La hipoxia intermitente mostró resultados beneficiosos en el crecimiento corporal y cantidad de neuronas en el área CA1 del hipocampo, en contraste, la hipoxia hiperoxia intermitente experimentó resultados adversos con disminución de estas variables, en el periodo postnatal temprano de la rata.

SUMMARY: The early postnatal period is characterized by rapid brain growth, possibly related to variations in tissue oxygen. This has motivated the study of protocols that supply different intermittent oxygen concentrations, to observe their morphological and cerebral effects. Fifty-two pups Sprague-Dawley rats were distributed in equal numbers into four experimental groups, Control (C, 21 %O), Intermittent Hypoxia (HI, 11 %O), Intermittent Hyperoxia (HOI, 30 %O2) and Intermittent Hypoxia Hyperoxia (HHI, 11 % - 30 %O2). The protocols considered 5 cycles of 5 min of dosing, for 50 min diary. It was performed in a semi- hermetic chamber between 5 to 11postnatal days. The evaluations of body growth and neuronal quantification were analyzed in male pups, on postnatal day 28. Body weight in the intermittent hypoxia group showed significant differences compared to the intermittent hyperoxia group (HI vs HOI, p<0.01) and the intermittent hypoxia- hyperoxia group (HI vs HHI, p<0.001). Body size decreased in the Intermittent hypoxia-hyperoxia group with significant differences compared to the control group (C vs HHI, p<0.05) and with respect to the intermittent hypoxia group (HHI vs HI, p<0.01). The neuronal count in the area CA1 of the hippocampus increased in the intermittent hypoxia group with significant differences compared to the control groups (C vs HI; p<0.05), to the intermittent hyperoxia group (HI vs HOI; p< 0.001) and the intermittent hypoxia-hyperoxia group (HI vs HHI; p<0.001). Finally, the intermittent hypoxia- hyperoxia group decreased significantly in the number of neurons compared with the intermittent hyperoxia group (HHI vs HOI; p<0.001). Intermittent hypoxia showed beneficial results in body growth and the number of neurons in the CA1 area of the hippocampus, in contrast, intermittent hypoxia-hyperoxia experienced adverse results with a decrease in these variables, in the early postnatal period of the rat.

Effects of estrogen and raloxifene on synaptic density in the hippocampal CA1 region of ovariectomized rats

Abstract Introduction The CA1 region of the hippocampus has an important role in learning and memory. It has been shown that estrogen deficiency may reduce the synaptic density in the region and that hormone replacement therapy may attenuate the reduction. Objectives This study aimed to evaluate the effects of estrogen and raloxifene on the synaptic density profile in the CA1 region of the hippocampus in ovariectomized rats. Methods Sixty ovariectomized three-month-old virgin rats were randomized into six groups (n = 10). Treatments started either three days (early treatment) or sixty days (late treatment) after ovariectomy. The groups received propylene glycol vehicle (0.5 mL/animal/day), equine conjugated estrogens (50 μg/animal/day), or raloxifene (3 mg/kg/day) either early or late after ovariectomy. The drugs were administered orally by gavage for 30 days. At the end of the treatments, the animals were anesthetized and transcardially perfused with ether and saline solution. The brains were removed and prepared for analysis under transmission electron microscopy and later fixed. Results Results showed a significant increase in the synaptic density profile of the hippocampal CA1 region in both the early estrogen (0.534 ± 0.026 µ/m2) and the early raloxifene (0.437 ± 0.012 µ/m2) treatment groups compared to the early or late vehicle-treated control groups (0.338 ± 0.038 µ/m2 and 0.277 ± 0.015 µ/m2 respectively). Conclusions The present data suggest that the raloxifene effect may be lower than that of estrogen, even early or late treatment, on synaptic density in the hippocampus.

CO2 laser moxibustion for endometriosis related pelvic pain of cold coagulation and blood stasis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical therapeutic effect of CO2 laser moxibustion on endometriosis related pelvic pain of cold coagulation and blood stasis.@*METHODS@#A total of 76 patients with endometriosis related pelvic pain of cold coagulation and blood stasis were randomized into a laser moxibustion group and a sham laser moxibustion group, 38 cases in each group. In the laser moxibustion group, moxibustion was applied at bilateral Zigong (EX-CA 1) using CO2 laser moxibustion instrument. In the sham laser moxibustion group, the manipulation of moxibustion was same as the laser moxibustion group, without laser output. The treatment was given once every other day, 30 min each time, 3 times a week for 4 weeks in both groups. Before and after treatment and follow-up of 3 months after treatment, the scores of Gracely box scale (GBS) and visual analogue scale (VAS) were observed, the usage of non-steroidal anti-inflammatory drug for the duration of the treatment and the average days of taking drugs were recorded in both groups.@*RESULTS@#Compared before treatment, the GBS and VAS scores were decreased after treatment and during follow-up in the laser moxibustion group (P<0.05), while those in the sham moxibustion group had no significant differences (P>0.05). Compared with the sham moxibustion group, the GBS and VAS scores were decreased after treatment and during follow-up (P<0.05), the cases and average days of taking drugs were less in the laser moxibustion group (P<0.05).@*CONCLUSION@#CO2 laser moxibustion can improve the pain symptom in patients with endometriosis related pelvic pain of cold coagulation and blood stasis, and reduce the use of analgesic drugs.

Effect of Zishen Huoxue Prescription on Regulation of Mitophagy and Neurogenesis in Hippocampal CA1 Region of Vascular Dementia Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Zishen Huoxue prescription on promoting neurogenesis in hippocampal CA1 region of vascular dementia （VD） rats by regulating mitophagy. MethodThe 2-VO method was used to establish the VD rat model and 60 SD rats were randomly divided into sham operation group， model group， donepezil hydrochloride group， and Zishen Huoxue prescription low-dose（8.9 g·kg-1）， medium-dose（17.8 g·kg-1） and high-dose（35.6 g·kg-1） groups. Morris water maze test was performed to detect the escape latency and the number of crossing platform in each group. The expression of phosphatase and tensin homology-induced kinase 1 （PINK1） and Parkinson protein （Parkin） mRNA in hippocampal CA1 region was detected by Real-time fluorescent quantitative polymerase chain reaction（Real-time PCR）. Western blot was used to determine the expression of mitochondrial autophagy signaling pathway-related proteins Parkin， prohibitin 2 （PHB2）， mitofusin 2 （Mfn2） and dynamin-related protein 1 （Drp1） in hippocampal CA1 region. The neurogenesis in hippocampal CA1 region was tested by Brdu method. ResultCompared with the conditions in the sham operation group， the learning and spatial memory abilities of the model group were decreased （P<0.05）， with damaged mitochondrial structure and autolysosome formation in the hippocampal CA1 region. The expressions of Parkin， Pink1 mRNA and Parkin， PHB2， and Drp1 proteins were up-regulated （P<0.05）， while the expression of Mfn2 protein and the neuronal regeneration in hippocampal CA1 region were reduced （P<0.05， P<0.05）. Compared with the conditions in the model group， Zishen Huoxue prescription enhanced the learning and spatial memory abilities of VD rats （P<0.05）， increased the number of autophagosomes in hippocampal CA1 region and improved the mitochondrial structure. The expression of Parkin， Pink1 mRNA and Parkin， PHB2， and Drp1 proteins in hippocampal CA1 region was up-regulated （P<0.05， P<0.01）while the expression of Mfn2 protein was down-regulated（P<0.05， P<0.01）. The number of new neurons in hippocampal CA1 region was also increased（P<0.05， P<0.01）. ConclusionThe promoting effect of Zishen Huoxue prescription on the neurogenesis in hippocampal CA1 region of VD rats was related to the mitophagy mediated by Pink1/Parkin signaling pathway.

Induction of long-term potentiation at Schaffer collateral-CA1 synapses in mice hippocampus after IMPX977 administration / 中草药·英文版

Objective: To investigate the effects of IMPX977 on long term potentiation (LTP) at Schaffer collateral-CA1 synapses in vitro and on methyl CpG binding protein 2 (Mecp2) expression in mice cortex and hippocampus. Methods: Thirty-two C57BL/6 mice were randomly divided into four groups: control, olive oil (vehicle), IMPX977 low (5 mg/kg) and high (15 mg/kg) groups. Mice were administrated every other day orally for two weeks. Extracellular recording technique in vitro was used to record the effects of IMPX977 on Schaffer collateral-CA1 LTP pathway in acute mice hippocampal slices. The Mecp2 protein expression level was detected by Western blotting. Results: Compared to the control group, vehicle did not alter the synaptic transmission in Schaffer collateral-CA1 synapses, however, IMPX977 at concentrations of 5 mg/kg and 15 mg/kg significantly enhanced fEPSP (field excitatory postsynaptic potential) slope in Schaffer collateral-CA1 pathway to (179.6 ± 17.8)% and (191.4 ± 21.4)%, individually 60 min after HFS, IMPX977 improved LTP induction significantly at Schaffer collateral-CA1 pathway at least. Also, IMPX977 significantly elevated MeCP2 protein level in cortex. Conclusion: The effects of IMPX977 on synaptic transmission and Mecp2 protein expression provided convincing evidence that IMPX977 could be promising new drug candidates for Rett syndrome treatment.

Effects of Beta; 1-adrenoceptors in the Basolateral Amygdala on Spatial Memory, Passive Avoidance, Long-term Potentiation and Neuronal Arborization in the Hippocampal CA1 Region in Response to Unavoidable Stress

Abstract Norepinephrine in the basolateral amygdala (BLA) plays a pivotal role in mediating the effects of stress on memory functions in the hippocampus, however, the functional contribution of β1-adrenergic receptors on the BLA inputs to the CA1 region of hippocampus and memory function are not well understood. In the present study the role of β1-adrenoreceptor in the BLA on memory, neuronal arborization and long-term potentiation (LTP) in the CA1 region of hippocampus was examined by infusion the β1-adrenoreceptor agonist (Dobutamine; 0.5µl/side) or antagonist (Atenolol; 0.25µL/side) bilaterally into the BLA before foot-shock stress. Passive avoidance test results showed that Step-through latency time was significantly decreased in the stress group rats one, four and seven days after the stress, which intra-BLA injection of Atenolol or Dobutamine before stress couldn't attenuate this reduction. Barnes-maze results revealed that infusion of Dobutamine and Atenolol significantly reduced spatial memory indicators such as increased latency time, the number of errors and the distance traveling to achieve the target hole in the stress group. These learning impairments in stress rats correlated with a reduction of LTP in hippocampal CA1 synapses in-vivo, which infusion of Dobutamine and Atenolol couldn't attenuate the population spike amplitude and mean-field excitatory postsynaptic potentials (fEPSP) slope reduction induced by stress. Also, the Golgi-Cox staining demonstrated that infusion of Atenolol attenuated stress decreased CA1 region dendritic and axonal arborization. These results suggest that β1-adrenergic receptors activation or block seem to exacerbate stress-induced hippocampal memory deficits and this effect is independent of CA1 LTP modulation.

Effect of Electroacupuncture on Synaptic Plasticity and 5-Htt Protein In Hippocampal Ca1 Region of WKY Depression Model Rats / 世界科学技术-中医药现代化

Objective: To observe the effects of electroacupuncture (EA) on depressive-like behavior, synaptic plasticity and 5-HTT protein expression of hippocampal CA1 region in the WKY model rats. Methods In this experiment, 10 male Wistar rats were selected as the normal group (Control), and 30 male WKY rats were randomly divided into model group, electroacupuncture group (EA) and sham needle group (Sham EA) . Behavioral testing was performed by the Sour Water Preference Experiment (SPT), the Open Field Experiment (OFT), and the Forced Swimming Experiment (FST) . The electrophysiological field potential experiment was used to detect the effect of electroacupuncture on LTP in the hippocampal CA1 region of rats with depression, which is the effect on synaptic plasticity. The expression of 5-HTT protein in hippocampal CA1 region was detected by Western blot. Results In the SPT, compared to the Control group, the sucrose solution intake was significantly reduced in the Model group (P ＜ 0.01) . It was improved after EA treatment compared to Sham EA group (P ＜ 0.05) . In the OFT, compared with the Control group, the center time, total move time, center distance, total distance, rearing and grooming incidents were all decreased in the Model group. Compared with the Model group, the center time and total move time in the EA group increased significantly after 3 weeks of treatment (P ＜0.05) . In the FST, duration of immobility was significantly (P ＜ 0.05) longer in the Model group comparing with the Control group. Compared with Sham EA group and Model group, the immobile time of EA group was significantly shorter (P ＜ 0.05) . Compared with the Control group, the fEPSP slope of the Model group was significantly shorter (P ＜ 0.001) .Compared with the Sham EA group, the fEPSP slope of the EA group increased significantly (P ＜ 0.001) . And the LTP of Sham EA and Model groups induced failure in hippocampal CA1 region, the LTP induction was successful after EA treatment. Compared with the Control group, the expression of 5-HTT protein was significantly increased (P＜0.001) .Compared with Sham EA group, the expression of 5-HTT protein in EA group decreased (P ＜ 0.001) . Conclusion EA could alleviate depression-like behaviors in depression model rats and reverse the impairment of hippocampus synaptic plasticity by decrease the over-expression of 5-HTT protein in hippocampal CA1 region. It may be one of the mechanisms of EA on depression.

Electroacupuncture plus Gastrodin Improves Learning-memory Ability Possibly by Up-regulating Expression of SIRT 1 and PGC-1 ɑ in Hippocampal CA 1 Region of Alzheimer's Disease Rats / 针刺研究

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.

Effect of Electroacupuncture on Learning-memory Ability in Rats with Hypoxic-ischemic Encephalopathy / 针刺研究

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.

Effects of Yinao Jieyu Prescription on the Behaviors and Damages of Pathology in Hippocampal CA1 Area of Rats with Post-stroke Depression / 中国中医药信息杂志

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.

Effects of Abnormal Phlegmatic Munziq on Ability of Learning and Memory and Protein Expressions of Brain Tissue RAGE and LRP1 of APP/PS1 Transgenic Mice Model of AD / 中国中医药信息杂志

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.

Clinical efficacy observation on treatment of primary dysmenorrhea with ginger-partitioned moxibustion at Zigong (EX-CA 1) / 针灸推拿医学（英文版）

Objective: To investigate the clinical effect of ginger-partitioned moxibustion at Zigong (EX-CA 1) for primary dysmenorrhea. Methods: A total of 112 patients with primary dysmenorrhea were randomized into an observation group and a control group according to their visiting sequence, 56 cases in each group. Patients in the observation group received ginger-partitioned moxibustion at Zigong (EX-CA 1), while patients in the control group received oral intake of analgesic. For both groups, treatment started 1 week before menstruation and lasted for 3 menstrual cycles, continued by a 3-month follow-up visit, then the clinical efficacy was evaluated. Results: By the end of treatment, symptom score in the observation group was lower than that in the control group, showing a statistical significance (P<0.05). After 3 months of treatment, the value of prostaglandin F2a (PGF2α), systolic-to-diastolic peak velocity ratio (S/D), resistance index (RI) and pulsatility index (PI) in the observation group were significantly higher than those in the control group, showing statistical significances (all P<0.01).The recovery rate in the observation group was higher than that in the control group, showing a statistical significance (P<0.05). Conclusion: Ginger-partitioned moxibustion at Zigong (EX-CA 1) for primary dysmenorrhea is a combination of the merits of warming function of moxibustion, dissipating function of ginger and stimulation of acupoint, and is better than oral intake of analgesic.

Temporal changes in mammalian target of rapamycin (mTOR) and phosphorylated-mTOR expressions in the hippocampal CA1 region of rat with vascular dementia

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.

Segregated Cell Populations Enable Distinct Parallel Encoding within the Radial Axis of the CA1 Pyramidal Layer

Numerous studies have implicated the hippocampus in the encoding and storage of declarative and spatial memories. Several models have considered the hippocampus and its distinct subfields to contain homogeneous pyramidal cell populations. Yet, recent studies have led to a consensus that the dorso-ventral and proximo-distal axes have different connectivities and physiologies. The remaining deep-superficial axis of the pyramidal layer, however, remains relatively unexplored due to a lack of techniques that can record from neurons simultaneously at different depths. Recent advances in transgenic mice, two-photon imaging and dense multisite recording have revealed extensive disparities between the pyramidal cells located in the deep and the superficial layers. Here, we summarize differences between the two populations in terms of gene expression and connectivity with other intra-hippocampal subregions and local interneurons that underlie distinct learning processes and spatial representations. A unified picture will emerge to describe how such local segregations can increase the capacity of the hippocampus to compute and process numerous tasks in parallel.

Is the NMDA Receptor of the CA1 Region Participated in the Amnesic Effect of Harmane?

Aims: In the present study, we investigated the influence of NMDA receptor agonist (N-methyl-d-aspartate) and antagonist (D-AP7) on amnesia induced by a β-carboline alkaloid, harmane. Methodology: Animals implanted with bilateral cannulae at the CA1 regions of the dorsal hippocampus and microinjected with glutamatergic drugs. One-trial step-down was used to assess memory acquisition and then, the hole-board method to assess exploratory behaviors in adult male NMRI mice. Results: The results revealed that pre-training intra-CA1 administration of NMDA (0.5 ng/mouse) and D-AP7 (0.25 and 0.5 ng/mouse) improved and impaired memory acquisition, respectively. Also, pre-training intra-peritoneal (i.p.) administration of harmane (12 mg/kg) decreased memory acquisition. Furthermore, pre-training intra-CA1 injection of sub-threshold dose of NMDA (0.02 ng/mouse) reversed, while non-significant dose of D-AP7 (0.125 ng/mouse) did not change impairment of memory acquisition induced by harmane (12 mg/kg, i.p.). Conclusion: In addition, all above doses of drugs did not alter locomotor activity. These results suggest that the CA1 NMDA receptors are involved in harmane-induced amnesia.

Effects of Abnormal Phlegmatic Temperament Granules on Behavioristics and Hippocampus Pathomorphism of APP/PS1 Transgenic Mice / 中国中医药信息杂志

Objective To investigate the effects of Abnormal Phlegmatic Temperament Granules on spatial learning and memory, histopathology morphological change in hippocampus CA1 zone; 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 (donepezil 0.92 mg/kg) group, Abnormal Phlegmatic Temperament Granules high-, medium-, and low-dose groups (3, 2, 1.5 g/kg), 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 learning and memory ability of mice were detected by Morris water maze test; pathomorphism in hippocampus CA1 zone was detected by HE staining method; changes of myelin sheath, microtubule, and microfilament in myelinated nerve of hippocampus CA1 zone were detected by electron microscope. Results Morris water maze test results showed that escape incubation period of APP/PS1 transgenic mice was significantly longer than the normal control group (P<0.01), and the original platform time was significantly shorter than normal control group (P<0.01); compared with model control group, Abnormal Phlegmatic Temperament Granules treatment groups escape latency time was significantly reduced (P<0.05, P<0.01). Space experiments and escape incubation period of Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups were significantly shortened (P<0.05, P<0.01), and spatial searching test showed that the times of mice in Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups passing through effective area increased (P<0.01). The integrity of HE staining pyramidal cell layer in the hippocampus CA1 zones of Abnormal Phlegmatic Temperament Granules high-, medium-, and low-dose groups was relatively good; cells arranged orderly; distribution was normal. Electron microscopic observation showed that compared with model control group, the hippocampus neurons nuclear had irregular shape; nuclear membrane was clear and complete; chromatin was clear; nucleolus was obvious; cell matrix was uniform; organelles were abundant; mitochondrial cristae was obvious; endoplasmic reticulum and free ribosomes were obvious. Conclusion Abnormal Phlegmatic Temperament Granules can improve spatial learning and memory in APP/PS1 mice, alleviate neuronal ultrastructure damage and ultimately improve cognitive function.

Inhibition and machanisms of total saponins from Panax notoginseng on apoptosis of hippocampal CA1 subfield neurons of rats following global cerebral ischemia / 中草药

Objective: To explore whether total saponins of Panax notoginseng (TSPN) can protect hippocampal CA1 subfield neurons against apoptosis following global cerebral ischemia via up-regulating the Bcl-2/Bax ratio and preventing Caspase-3 activation. Methods: Using four-vessel occlusion method to build the global cerebral ischemia model and the ischemia time was 30 min. All rats were divided into Sham group, vehicle group, and different doses (25, 50, 75, and 100 mg/kg) of TSPN groups. The rats in TSPN groups were ip administered with TSPN. The dose of TSPN was suspended in 0.9% saline (10 g/L), while rats in vehicle group were treated with equal volume of 0.9% saline, one injection per day. Compared the survival rate and hippocampal CA1 subfield neuronal density by Nissl staining after reperfusion of 14 d to make sure the best dose of TSPN for neuroprotection. Then to evaluate the neurological score and investigate the expression level of the Caspase-3, Bcl-2, and Bax in the hippocampus CA1 region at days 1, 3, 7, and 14 post-ischemia by immunohistochemistry; In addition, the Western-blotting was adopted to test the protein level of these three proteins. Results: The survival rate of the rats in 75 mg/kg TSPN groups was 100%, and its neuronal density was significantly higher than that in vehicle group and other doses of TSPN groups (P < 0.05); The neurological score in TSPN group was significantly less than that in vehicle group (P < 0.01); The Caspase-3 neuronal density in the CA1 subfield of TSPN group on days 7 and 14 was significantly less than that in vehicle group (P < 0.001); The statistical meaning existed about the protein level of Caspase-3 with molecular weight of 20 000 on days 3, 7, and 14 and 17 000 on days 7 and 14 in two groups (P < 0.001). The neuronal density of Bcl-2 cells in the CA1 subfield and Bcl-2 protein level in the hippocampus of TSPN group at days 7 and 14 was significantly higher than that in vehicle group (P < 0.001); Besides, the Bax neuronal density at days 7 and 14 was significantly lower than that in vehicle group (P < 0.001); And its protein level of the hippocampus was less than that in vehicle group at days 3, 7 and 14 (P < 0.001). The results of ratio of Bcl-2/Bax from not only the neuronal density but also the protein expression demonstrated that the Bcl-2/Bax ratio in TSPN group was significantly higher than that in vehicle groups on days 7 and 14 (P < 0.001). Conclusion: TSPN can protect the hippocampal CA1 subfield neurons against apoptosis following global cerebral ischemia in adult rats via up-regulating the Bcl-2/Bax ratio and preventing Caspase-3 activation.

A Comparative Study of the Histological Changes in Cerebral Cortex, Hippocampus, Cerebellum, Pons & Medulla of the Albino Rat Due to Lead Toxicity.

Introduction: Lead, a heavy metal is well known for its toxic effects on the central nervous system. Clinically, overall effects of lead on different organ system are called plumbism. Diverse writing can be seen on the subject, but rarely there has been a comparison in any of these writings on different parts within the brain of the changes happening as the result of lead exposure. This study was taken up to draw a comparison and correlation of damaging effects on different parts of brain at microscopic level as a result of lead toxicity so that the affected elements in the tissue can be further connected to the histopathological and clinical outcomes of the lead toxicity. Materials and Methods: To conduct the study albino rats of Charles Foster strain were administered orally with 4% lead acetate in drinking water. The behavioral and clinical changes during the period of lead administration were closely observed that extended from irritability, agitation and aggressive behavior in the beginning to drastic fall in activity, indifference towards varieties of stimulus and severe motor deficit. At the end of an average of 17 days the rats were sacrificed for both gross and microscopic examination of brain for changes in the cerebral cortex, hippocampus, cerebellum, pons & medulla. The elements of the tissue observable as per the selected staining were the neurons, fibers, glia & the vessels. Results: The changes showed up with similarities between different parts as the shrinkage of neurons, damaged fibers, stunting of cell processes and increased glial cell population, whereas there were dissimilarities with regards to the extent of shrinkage of neuron and distribution of perineuronal spaces, vacuoles & the glial cells. Discussion and Conclusion: The comparative picture of the changes as a result of lead exposure showed widespread damage to nearly all the elements of the nervous tissue with reactive changes e.g. gliosis, and variations in the extend of changes in the selected brain parts. As a result these changes observed can be of used to correlate in the overall outcome of plumbism in relation to the functions of different parts of the brain.

Effects of Modafinil on Behavioral Learning and Hippocampal Synaptic Transmission in Rats / 대한배뇨장애요실금학회지

PURPOSE: Modafinil is a wake-promoting agent that has been proposed to improve cognitive performance at the preclinical and clinical levels. Since there is insufficient evidence for modafinil to be regarded as a cognitive enhancer, the aim of this study was to investigate the effects of chronic modafinil administration on behavioral learning in healthy adult rats. METHODS: Y-maze training was used to assess learning performance, and the whole-cell patch clamp technique was used to assess synaptic transmission in pyramidal neurons of the hippocampal CA1 region of rats. RESULTS: Intraperitoneal administration of modafinil at 200 mg/kg or 300 mg/kg significantly improved learning performance. Furthermore, perfusion with 1mM modafinil enhanced the frequency and amplitude of spontaneous postsynaptic currents and spontaneous excitatory postsynaptic currents in CA1 pyramidal neurons in hippocampal slices. However, the frequency and amplitude of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons were inhibited by treatment with 1mM modafinil. CONCLUSIONS: These results indicate that modafinil improves learning and memory in rats possibly by enhancing glutamatergic excitatory synaptic transmission and inhibiting GABAergic (gamma-aminobutyric acid-ergic) inhibitory synaptic transmission.

Phasic and tonic type A γ‑Aminobutryic acid receptor mediated effect of Withania somnifera on mice hippocampal CA1 pyramidal Neurons.

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.