Platform Quadrant Research Articles

The Comparison of the Effects of Different Transcranial Electrical Stimulation (tES) Paradigms on Beta-Amyloid (Aβ 25-35)-Induced Memory Impairment upon Morris Water Maze Task in Male Rats

Background: In light of therapeutic limitations in Alzheimer's disease (AD), recent alternative or add-on treatment approaches such as non-invasive brain stimulation through transcranial electrical stimulation (tES) have gained attention. Translational studies have postulated that transcranial direct current stimulation (tDCS) is potentially a novel therapeutic option to reverse or stablize cognitive impairments. The aim of this study was to comparatively evaluate the effects of the four main paradigms of tES, including tDCS, transcranial alternative current stimulation (tACS), transcranial random noise stimulation (tRNS), and transcranial pulse current stimulation (tPCS) on beta amyloid 25-35 (Aβ 25-35)-induced memory impairment in male rats submitted to the Morris water maze (MWM) task. Method: To develop AD model in Sprague-Dawley male rats weighing 250-270, the cannula was implanted bilaterally into the hippocampi. Aβ 25-35 (5 μg/2.5 ml/ day) was microinjected bilaterally for 4 days. Then, tES was applied to the animals for 6 days. Subsequently, rats’ learning and memory function was evaluated on day 11-14 in MWM task. Results: Our findings indicated that tDCS, tACS, tRNS reduced escape latency, while such an effect was not observed in tPCS paradigm. In terms of the duration of animals’ presence in the platform quadrant, tDCS and tACS increased the outcome measure. Conclusion: We conclude that tDCS and tACS are more effective than the other two examined paradigms of tES in ameliorating learning and memory impairments.

Cognitive deficits and Alzheimer-like neuropathological impairments during adolescence in a rat model of type 2 diabetes mellitus.

Numerous studies have shown that many patients who suffer from type 2 diabetes mellitus exhibit cognitive dysfunction and neuronal synaptic impairments. Therefore, growing evidence suggests that type 2 diabetes mellitus has a close relationship with occurrence and progression of neurodegeneration and neural impairment in Alzheimer's disease. However, the relationship between metabolic disorders caused by type 2 diabetes mellitus and neurodegeneration and neural impairments in Alzheimer's disease is still not fully determined. Thus, in this study, we replicated a type 2 diabetic animal model by subcutaneous injection of newborn Sprague-Dawley rats with monosodium glutamate during the neonatal period. At 3 months old, the Barnes maze assay was performed to evaluate spatial memory function. Microelectrodes were used to measure electrophysiological function in the hippocampal CA1 region. Western blot assay was used to determine expression levels of glutamate ionotropic receptor NMDA type subunit 2A (GluN2A) and GluN2B in the hippocampus. Enzyme-linked immunosorbent assay was used to determine levels of interleukin-1β, tumor necrosis factor α, and interleukin-6 in the hippocampus and cerebral cortex, as well as hippocampal amyloid beta (Aβ)1-40 and Aβ1-42 levels. Our results showed that in the rat model of type 2 diabetes mellitus caused by monosodium glutamate exposure during the neonatal period, latency was prolonged and the number of errors increased in the Barnes maze. Further, latency was increased and time in the escape platform quadrant shortened. Number of times crossing the platform was also reduced in the Morris water maze. After high frequency stimulation of the hippocampus, synaptic transmission was inhibited, expression of GluN2A and GluN2B were decreased in the hippocampus, expression of interleukin 1β, interleukin 6, and tumor necrosis factor α was increased in the hippocampus and cortex, and levels of Aβ1-40 and Aβ1-42 were increased in the hippocampus. These findings confirm that type 2 diabetes mellitus induced by neonatal monosodium glutamate exposure results in Alzheimer-like neuropathological changes and further causes cognitive deficits and neurodegeneration in young adulthood.

Conditioned inhibition in the spatial domain in humans and rats

Spatial learning has been shown to follow associative rules by demonstrations of blocking and overshadowing in both watermazes with rats and virtual watermazes with humans. To examine whether Conditioned Inhibition (CI) can also be demonstrated in a real and virtual watermaze task, two studies were run, one with rats and one with humans. In separate training trials, Beacons A and B marked the position of a platform in quadrant X of circular watermaze (AX+/BX+). In subsequent inhibitory training trials, Beacon A was placed in quadrant Y with no platform present (AY−). To test for any CI of Y, in two probe trials B was suspended above either quadrant Y (BY) or novel quadrant Z (BZ). Time spent under B was recorded in both trials. In both animal and human studies, during no platform probe trials, latencies to reach Beacon B were longer and less time was spent under the beacon when it was suspended in quadrant Y, where inhibitory training had previously taken place (AY− trials), than when it was hung in the novel quadrant Z. Results suggest that quadrant Y had become a conditioned inhibitor strengthening claims that learning in the spatial domain follows the rules of associative models.

Inhibiting mammalian target of rapamycin signaling pathway improves cognitive function in mice with chronic cerebral ischemia

To investigate the effect of mammalian target of rapamycin(mTOR) inhibitor-rapamycin on cognitive function after chronic cerebral ischemia in mice and its molecular mechanism. The chronic cerebral ischemia model was induced by ligation of right common carotid artery (rUCCAO) in 6-week-old ICR mice. The expressions of mTOR, S6K, S6 and corresponding phosphorylated proteins were detected by Western blotting at different time interval (1 h, 3 h, 6 h, 24 h, 3 d, 7 d, 2 w, 4 w, 6 w) after rUCCAO to determine the changes of mTOR signaling pathway. Rapamycin was administrated i.p. at the dose of 3.0 mg/kg 24 h after rUCCAO. Fluoro Jade B staining was used to detect the apoptotic cells. The expressions of Beclin and LC3-Ⅱ were detected by Western blotting to determine the status of autophagy. Morris water maze test and Y maze test were performed to evaluate cognitive functions. The mTOR signaling pathway was abnormally activated from 6 h to 6 w after rUCCAO in mouse cortex. The activation of mTOR signaling pathway induced by rUCCAO was reversed by administration of rapamycin, and the apoptotic cell number was significantly decreased (146.1±16.3 vs 84.5±9.6, P<0.05). Meanwhile, the elevation of Beclin and LC3-Ⅱ protein induced by rUCCAO was reversed by rapamycin administration. Furthermore, compared with vehicle-treated mice, the latent period[(11.1±2.3) s vs (8.1±1.8) s, P<0.05] and swimming distance[(672.8±128.5) cm vs (558.2±124.9) cm, P<0.05] were significantly decreased and the number of crossing the platform quadrant in Morris water maze increased(2.8±0.9 vs 5.2±0.8, P<0.05) in rapamycin-treated mice. Correct response rate in the Y maze was also increased significantly in rapamycin-treated mice[(38.5±9.2)% vs (64.9±7.9)%, P<0.05]. Inhibiting mTOR pathway by rapamycin reverses the rUCCAO-induced cognitive impairment partly through the suppression of apoptosis and autophagy.

Effects of "nourishing liver and kidney" acupuncture therapy on expression of brain derived neurotrophic factor and synaptophysin after cerebral ischemia reperfusion in rats.

The aim of the present study was to investigate the effect of "nourishing liver and kidney" acupuncture therapy on motor and cognitive deficits, and the underlying mechanism following cerebral ischemia-reperfusion (I/R) via increasing the expression of brain derived neurotrophic factor (BDNF) and synaptophysin (SYN) in the hippocampus. Healthy adult male SD rats were randomly divided into sham operation group (n=51), model group (n=51), acupuncture group (n=51) and acupuncture control group (n=51). The middle cerebral I/R model was established. Acupunctures were performed in the acupuncture group and acupuncture control group at acupoints of Taixi (K103), Taichong (ST09) of both sides, for 30 min once daily every morning. The animals in the sham operation group and model group were conventionally fed in the cage, without any intervention therapy. The rats of each group were assessed with modified neurological severity scores (mNSS). The expression of BDNF and SYN in the hippocampus was detected by immunohistochemical SP method and the synaptic structure in hippocampus area was assessed morphologically and quantitatively at the 3rd, 7th and 14th day. The Morris water Maze (MWM) test was used to evaluate the rats' learning and memory abilities on the 15th day after acupuncture. The animals in the acupuncture control group and sham operation group presented no neurological deficit. In the acupuncture group, the nerve functional recovery was significantly better than that in the model group at the 7th and 14th day after modeling. The average MWM escape latency in the acupuncture group was shorter than that in the model group at the 3rd, 4th and 5th day. The number of crossings of the platform quadrant in the acupuncture group was significantly more than that in the model group. At the each time point, the expression levels of BDNF and SYN in the hippocampal regions increased significantly in the model group as compared with the sham operation group and the acupuncture control group. In the acupuncture group, the expression levels of BDNF at the 7th and 14th day increased more significantly than those in the model group. In the acupuncture group, the expression levels of SYN at the each time point increased more significantly than those in the model group. The post-synaptic density (PSD) was significantly increased and the synapse cleft width was narrowed in the acupuncture group as compared with other groups. The synaptic curvatures were improved obviously in the acupuncture group in contrast to the model group. It was concluded that the "nourishing liver and kidney" acupuncture therapy has positive effects on behavioral recovery, as well as learning and memory abilities, probably by promoting the expression of BDNF and SYN, and synaptic structure reconstruction in the ipsilateral hippocampus after I/R in rats. The "nourishing liver and kidney" acupuncture therapy can promote the functional recovery in rats after cerebral ischemia injury.

Effect of sevoflurane on expression of α7 nicotinic acetylcholine receptor in hippocampal neurons of rats

Objective To evaluate the effect of sevoflurane on the expression of α7 nicotinic acetylcholine receptor (α7nAChR) in hippocampal neurons of rats. Methods Forty-eight pathogen-free healthy adult Sprague-Dawley rats of both sexes, weighing 210-280 g, aged 3-4 months, were divided into 4 groups (n=12 each) using a random number table: control group (group C) and 1%, 3% and 5% sevoflurane groups (S1, S2 and S3 groups). In S1, S2 and S3 groups, 1%, 3% and 5% sevoflurane were inhaled for 1 h, respectively.Morris water maze test was performed at 1 and 7 days after anesthesia to assess the cognitive function.Six rats in each group were sacrificed after the end of the test.The brains were then removed and the hippocampi were isolated for detection of the expression of α7nAChR (by Western blot) and contents of tumor necrosis factor-alpha and interleukin-1 (by enzyme-linked immunosorbent assay). Results Compared with group C, the number of crossing the platform was significantly decreased at 1 and 7 days after anesthesia in group S1, the time of staying at the target quadrant was significantly shortened, the number of crossing the platform was decreased, and the rate of time of staying at the original platform quadrant and rate of swimming distance at the original platform quadrant were decreased at 1 and 7 days after anesthesia in S2 and S3 groups, and the contents of tumor necrosis factor-alpha and interleukin-1 were significantly increased, and the expression of α7nAChR was down-regulated at 1 and 7 days after anesthesia in S1, S2 and S3 groups (P 0.05). Conclusion The mechanism by which sevoflurane induces inflammatory responses in hippocampi is related to down-regulation of α7nAChR expression in hippocampal neurons of rats. Key words: Anesthetics, inhalation; Receptors, cholinergic; Hippocampus; Neurons; Cognition disorders; Postoperative complications

Effect of isoflurane preconditioning on expression of hippocampal GluR1 subunits-containing AMPA receptors in a rat model of focal cerebral ischemia-reperfusion

Objective To evaluate the effect of isoflurane preconditioning on the expression of hippocampal GluR1 subunits-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate(AMPA)receptors in a rat model of focal cerebral ischemia-reperfusion(I/R). Methods Forty-eight pathogen-free healthy male Sprague-Dawley rats, weighing 250-280 g, aged 7-8 weeks, were divided into 3 groups(n=16 each)using a random number table: sham operation group(group S), focal cerebral I/R group(group I/R)and isoflurane preconditioning group(group IPC). Focal cerebral I/R was induced by occlusion of the middle cerebral artery for 2 h followed by reperfusion to induce cognitive decline in I/R and IPC groups. Rats were exposed to 1.5% isoflurane for 1 h every day for 5 consecutive days, and the model was established at 24 h after the last exposure in group IPC. Eight rats in each group were selected to perform Morris water maze test for 6 consecutive days starting from 9 or 23 days after operation. The rats were sacrificed at 14 and 28 days after operation, and the hippocampal tissues were obtained for determination of the expression of GluR1 mRNA(by using real-time polymerase chain reaction)and GluR1 protein(by Western blot). Results Compared with group S, the escape latency was significantly prolonged at each time point after operation, the frequency of crossing the original platform quadrant and percentage of swimming distance at the original platform quadrant were decreased at 14 and 28 days after operation, and the expression of GluR1 protein and mRNA was down-regulated at 14 days after operation in I/R and IPC groups(P<0.05). Compared with group I/R, the escape latency was significantly shortened at 10-13 days after operation, the percentage of swimming distance at the original platform quadrant and frequency of crossing the original platform quadrant were increased at 14 days after the operation, and the expression of GluR1 protein and mRNA was up-regulated at 14 days after operation in group IPC(P<0.05). Conclusion The mechanism by which isoflurane preconditioninig improves the cognitive function is related to up-regulation of the expression of hippocampal GluR1 subunits-containing AMPA receptors in a rat model of focal cerebral I/R. Key words: Isoflurane; Ischemic preconditioning; Brain; Reperfusion injury; Hippocampus; Receptors, AMPA

Effect of sevoflurane on hippocampal cAMP-PKA-CREB signaling pathway in aged rats

Objective To evaluate the effect of sevoflurane on hippocampal cyclic AMP (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB) signaling pathway in aged rats. Methods Sixty healthy aged male Sprague-Dawley rats, aged 18 months, weighing 600-750 g, were divided into control group (C group, n=30) and sevoflurane group (group Sev, n=30) using a random number table method.Group Sev inhaled 2% sevoflurane for 4 h. Group C inhaled the mixture of 50% air and oxygen (2 L/min) for 4 h. Morris water maze test was performed on 1-6 days before anesthesia and at 1 day after the end of anesthesia (at the corresponding time points in group C). The animals were sacrificed and hippocampi were removed at 1, 3 and 7 days after anesthesia (at the corresponding time points in group C) for determination of the hippocampal cAMP content (using enzyme-linked immunosorbent assay) and expression of hippocampal CREB, phosphorylated CREB (p-CREB) and PKA (using Western blot), and the p-CREB/CREB ratio was calculated. Results Compared with group C, the escape latency and swimming distance were significantly prolonged, the frequency of crossing the original platform was decreased, the time of staying at the original platform quadrant was shortened at 1 day after the end of anesthesia, and the expression of hippocampal cAMP and PKA was down-regulated at 1, 3 and 7 days after the end of anesthesia, and the expression of CREB and p-CREB was down-regulated and p-CREB/CREB ratio was decreased at 1 day after the end of anesthesia in group Sev (P<0.05). Conclusion The mechanism of sevoflurane-induced postoperative cognitive dysfunction may be related to inhibiting hippocampal cAMP-PKA-CREB signaling pathway in aged rats. Key words: Cyclic AMP; Cyclic AMP-dependent protein kinases; Cyclic AMP response element-binding protein; Anesthetics, inhalation; Cognition disorders

Behavioral Changes and Hippocampus Glucose Metabolism in APP/PS1 Transgenic Mice via Electro-acupuncture at Governor Vessel Acupoints

Objective: Investigating the effects of electro-acupuncture (EA) treatment on mice with Alzheimer’s disease (AD), using Morris water maze (MWM) for spatial learning and memory behavior tests combined with micro-positron emission tomography (micro-PET) imaging for glucose metabolism in hippocampus.Methods: Thirty seven-month-old APP/PS1 mice were randomly divided into AD Model group (AD group), medicine group (M group) and EA group, C57BL/6 mice were used for Normal control group (N group), n = 10 in each group. Mice in M group received donepezil intervention by gavage with dose at 0.92 mg/kg. EA was applied at Baihui (GV20) and Yintang (GV29) acupoints for 20 min then pricked at Shuigou (GV26) acupoint, while mice in N, M and AD groups were received restriction for 20 min, with all treatment administrated once a day for 15 consecutive days. After the treatment, MWM was performed to observe behavioral changes in mice, then hippocampus glucose metabolism level was tested by micro-PET imaging.Results: Compared with that of AD group, the escape latency of M and EA groups declined significantly (P < 0.01), while the proportion of the platform quadrant swimming distance in total swimming distance showed an obvious increase (P < 0.01), and EA group occupied a higher percentage than that in M group. The micro-PET imaging showed that mice in AD group performed a lower glucose metabolic rate in hippocampus compared with N group (P < 0.01). Both M and EA groups presented a significant higher injected dose compared with AD group (P < 0.01), and the uptake rate of EA group was higher than M group.Conclusion: Both donepezil and EA have therapeutic effects on AD mice. To a certain extent, EA shows a better efficacy in treatment of AD by improving the spatial learning and memory ability, while also enhancing glucose metabolism in hippocampus.

An ontogenic study of the behavioral effects of chronic intermittent exposure to ayahuasca in mice.

Ayahuasca is a beverage obtained from decoctions of the Banisteriopsis caapi plus Psychotria viridis. In religious contexts, ayahuasca is used by different age groups. However, little is known of the effects of ayahuasca during ontogenic development, particularly with regard to the functional characteristics of the central nervous system. Animal models are useful for studying the ontogenic effects of ayahuasca because they allow exclusion of the behavioral influence associated with the ritualistic use. We investigated the effects of exposure to ayahuasca (1.5 mL/kg, orally, twice a week) on memory and anxiety in C57BL/6 mice, with the post-natal day (PND) being used as the ontogenic criterion for classification: childhood (PND21 to PND35), adolescence (PND35 to PND63), adulthood (PND90-PND118), childhood-adolescence (PND21 to PND63), childhood-adulthood (PND21 to PND118) and adolescence-adulthood (PND35 to PND118). One day after the last ayahuasca exposure, the mice were subjected to the Morris water maze (MWM), open field and elevated plus maze tasks (EPM). Ayahuasca did not affect locomotion in the open field or open arms exploration in the EPM, but increased the risk assessment behavior in the childhood group. Ayahuasca did not cause any change in acquisition of spatial reference memory in the MWM task, but decreased the time spent on the platform quadrant during the test session in the adolescence group. These results suggest that, in mice, exposure to ayahuasca in childhood and adolescence promoted anxiety and memory impairment, respectively. However, these behavioral changes were not long-lasting since they were not observed in the childhood-adulthood and adolescence-adulthood groups.

Ginsenosides attenuate d-galactose- and AlCl3-inducedspatial memory impairment by restoring the dysfunction of the neurotransmitter systems in the rat model of Alzheimer's disease

Ethnopharmacological relevancePanax ginseng C.A.Mey. is a traditional Chinese herbal medicine, which has been used to treat Alzheimer's disease (AD) for thousands of years. Ginsenoside is one of the major compounds found in P. ginseng. This study aimed to explore the attenuation of spatial memory impairment by ginsenosides and its correlation with restoring the dysfunction of the neurotransmitter systems in AD model rats to understand the mechanism underlying the anti-AD effect of P. ginseng. Materials and methodsIn this study, the AD model was established by combining d-galactose (d-gal) with AlCl3 (Al) for 60 days. From day 30, the ginsenosides group was intragastrically administered with ginsenosides for 30 days. The ethology of rats was tested through the Morris water maze test(MWM). Histopathological changes in the hippocampus of rats were observed through hematoxylin and eosin staining. The expressions of amyloid β peptide (Aβ) and phospho-tau (p-tau) in the hippocampus and cortex of rats were detected by immunohistochemistry. A liquid chromatography–mass spectrometry assay was used to measure neurotransmitter concentrations in the hippocampus, cortex, and blood. ResultsGinsenosides could significantly decrease the escape latency time and the average latency time in the place navigation test and increase the times of crossing the platform area, the percentage of residence time, and the distance in the original platform quadrant in the spatial probe test. Ginsenosides could repair the damage of the hippocampus and reduce the expressions of Aβ and p-tau. Ginsenosides could also increase γ-aminobutyric acid, acetylcholine, and dopamine levels and decrease glutamate and aspartic acid levels in the hippocampus and cortex and increase glycine and serotonin levels in the blood. ConclusionsAfter effectively administrated, ginsenosides attenuate d-gal- and Al-induced spatial memory impairment. The possible mechanism of the beneficial effect is restoring the dysfunction of various neurotransmitters.

High Cholesterol Diet Increases Expression of Cholesterol 24-Hydroxylase and BACE1 in Rat Hippocampi: Implications for the Effect of Diet Cholesterol on Memory

Background: Abnormal cholesterol homeostasis is associated with the pathogenesis of neurodegenerative disease and cognitive impairment. Objectives: Our objective was to evaluate changes in the expression of proteins related to cognition and cholesterol homeostasis in the hippocampi of rats as well as behavioral modifications following the administration of a cholesterol-rich diet. Methods: In this experimental study, lasting 16 weeks, 20 male Wistar rats (aged 8 weeks) were randomly divided into two groups. One group was fed with a normal diet (ND; n = 10) and the second with a high cholesterol diet (HD; n = 10). The expression of the cognition-related proteins N-methyl-D-aspartate receptor (NMDAR) and beta-secretase 1 (BACE1) and cholesterol 24-hydroxylase (CYP46A1), the key cholesterol hemostasis protein, were determined by an immunoblotting assay in the hippocampus homogenate. The Morris water maze (MWM) test was used to examine cognitive performance. Plasma lipidic parameters, including total choles- terol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG), as well as brain TC were measured by colorimetric assay. Results: After a high cholesterol diet had been administered for a period of 16 weeks, a significant increase in TC, LDL-C and TG was observed in the HD group in comparison with the ND group (P < 0.05). Neither the mean of brain wet weight nor brain TC showed significant change in the HD versus the ND group (P = 0.114, P = 0.84, respectively). Despite this fixity, dierences in the expression of BACE1 and CYP46A1 were significant (P < 0.05) between the two groups, with high levels of BACE1 and CYP46A1 in the HD group compared with the ND group. These biochemical changes were associated with a significant decrease in the time traveled on a platform quadrant in the HD versus the ND group (P < 0.05) during a spatial memory probe test administered at the same time. Conclusions: The findings show that irregularities in cognitive performance as a result of a high cholesterol diet can be partially mediated by distortion in brain cholesterol homeostasis and processing of the amyloid precursor protein (APP).

Polysaccharides from Pleurotus ostreatus alleviate cognitive impairment in a rat model of Alzheimer’s disease

This study was conducted to evaluate the effects of polysaccharides extracted from Pleurotus ostreatus (POP) on d-galactose and AlCl3-induced cognitive impairments. A behavioral test suggested that POP significantly decreased escape latency and increased crossing parameters of platform quadrant in a Morris water maze test. Furthermore, POP decreased error numbers and increased passive avoidance latency in a step-down test. Biochemical examinations revealed that POP significantly elevated superoxide dismutase, glutathione peroxidase, and catalase activities; and reduced malondialdehyde levels and acetylcholinesterase activity. Moreover, POP could decrease amyloid β peptide formation and tau phosphorylation by elevating the expression of protein phosphatase 2A as well as by reducing the expression of amyloid precursor protein (APP), β-site APP clearing enzyme1, and glycogen synthase kinase 3beta. These findings provide scientific evidence to support the exploitation of POP as a safe and effective drug to prevent and treat Alzheimer’s disease.

Salvianolic acid improves cognitive function in rats with depression

Objective To investigate the effect of salvianolic acid on cognitive function in rats with depression. Methods 92 SD male rats were randomly divided into 5 groups: non stress+ saline(control group, n=19), stress+ saline (saline group, n=19), stress+ fluoxetine (fluoxetine group, n=18), stress+ salvianolic acid (salvianolic acicl group, n=20) and stress+ salvianolic acid+ fluoxetine (combination group, n=16). Chronic mild stress was used to establish depression model in rats. When models were successfully established, fluoxetine 20 mg·kg-1(A), salvianolic acid 40 mg·kg-1(B), combination of A and B and 0.9% sodium chloride were given by intraperitoneal injection respectively, the volume to body weight ratio was 10 ml·kg-1. After 3 weeks of stress and drug administration, the added weight (g) and sucrose preference rate (%) were measured. The Morris water maze (MWM) test was adopted after 3 weeks' stress and 3 weeks' drugs injection to evaluate the change of cognitive function. Results After 3 weeks' stress, a significant difference was found among 5 groups(F=11.828, P<0.01) and the added weight of control group was higher than other groups(all P<0.05). There was significant difference of the mean of average escape latency among 5 groups' rats during the first 5 days of MWM(F=5.732, P<0.01), and difference was found in the measurements of the time (F=136.000, P<0.01). The average escape latency of control group was lower (all P<0.05), and the time of across the platform quadrant were longer than those of other groups (all P<0.01). After 3 weeks' drug injection, the added weight in saline group was lower than that of the groups of fluoxetine, salvianolic acid and combination(all P<0.01). The sucrose preference rate in the groups of fluoxetine, salvianolic acid, and combination group was lower than that of saline group(all P<0.01). In MWM test, the difference of average avoid latency was existed in the five groups of the first 5 days (F=16.243, P<0.01). Similarly, there was a significant difference in measure time (F=9.359, P<0.01). And a significant difference was found in crossing the platform quadrant in the 6th day of MWM (F=14.499, P<0.01). Compared with saline group((9.39±2.22)s), the time crossing the platform quadrant at sixth day in the control group((16.93±4.49)s), fluoxetine group((16.89±3.99)s), salvianolic acid group((13.82±4.77)s) and combination group((18.74±4.63)s) were increased(all P<0.01). The time of crossing platform quadrant in combination group was higher than that of salvianolic acid group(P<0.05). Conclusion Salvianolic acid can improve cognitive function in depression rats. Key words: Salvianolic acid; Depression; Cognitive function; Chronic mild stress; Water maze

Effects of dl-3n-butylphthalide on study and memory abilities and hippocampus expression of MMP-9 in rat model of radiation injuries of brain

Objective To study the effects of dl-3n-butylphthalide on study and memory abilities and hippocampus expression of MMP-9 in rat model of radiation injuries of brain. Methods Wistar rats were divided into radiation group radiated by linear accelerator and control group . Morris water test were taken to study the learning and memory ability of rats in each group before irradiation and 120 d after irradiation. Results Morris water maze test results showed that: in the academic test, compared with model group, high-dose butylphthalide group and low dose butylphthalide group had significantly shorter escape latency((79.61±7.17)s, (43.64±4.72)s, (42.15±4.19)s) and decreased number of errors(36.43±6.59, 14.58±4.22, 13.66±3.91)(P<0.01). In the memory test, compared with model group, high-dose butylphthalide group and low dose butylphthalide group had significantly longer the former platform quadrant time respectively (30.09±3.68)s, (31.25±3.17)s vs (17.57±4.29)s and faster swimming speed respectively(P<0.01). Conclusion Butylphthalide can significantly reduce hippocampal neurons' expression of MMP-9, which indicates that butylphthalide has curative effect on radiation brain injuries by regulating the expression of MMD-9. Key words: Butylphthalide; Radiation brain injuries; Learning and memory; Rat

Hyperbaric oxygen therapy can improve the learning capacity and memory in vascular dementia

Objective To explore the influence of hyperbaric oxygen therapy (HBOT) on the learning and memory ability using a rat model of vascular dementia (VD). Methods Sixty Sprague-Dawley rats were selected and divided into a normal group, a sham operation group, a VD group and an HBOT group, each of 15 rats using a random number table. The improved four-vessel method was used to establish a VD model in all except the rats in the normal group, but for the sham operation group, the vertebral artery was not subjected to firing and the arteria carotis communis was not clipped. The HBOT group was then given HBOT for 7 days. The Morris water maze test was used to evaluate their learning and memory ability of all 4 groups. Results Compared to the normal group, the mean escape latency of the sham operation group, the VD group and the HBOT group was significantly longer in each case (P<0.05). Their platform quadrant crossing times were also significantly less, and their quadrant swimming distance as a proportion of their total swimming distance was significantly smaller (P<0.05). Compared with the sham operation group, the mean escape latency of the VD and HBOT groups was significantly longer (P<0.05), the times of crossing platform quadrant were less and their quadrant swimming distance was a smaller proportion of their total swimming distance. As compared with the VD group, the mean escape latency of the HBOT group was significantly shorter [(25.73±6.20) s], the average platform quadrant crossing times were significantly more [(9.51±2.25) times] and the platform quadrant swimming distance of the HBOT group was significantly longer [(494.72±208.26)], representing a significantly larger proportion of the total swimming distance [(28.71±5.32)%](P<0.05). Conclusion HBOT can effectively improve learning and memory in vascular dementia, at least in rats. Key words: Hyperbaric oxygen therapy; Vascular Dementia; Morris water maze; Learning; Memory

Effects of Hydrogen-Rich Saline on Hepatectomy-Induced Postoperative Cognitive Dysfunction in Old Mice.

This study aims to investigate the protective effects and underlying mechanisms of hydrogen-rich saline on the cognitive functions of elder mice with partial hepatectomy-induced postoperative cognitive dysfunction (POCD). Ninety-six old male Kunming mice were randomly divided into 4 groups (n = 24 each): control group (group C), hydrogen-rich saline group (group H), POCD group (group P), and POCD + hydrogen-rich saline group (group PH). Cognitive function was subsequently assessed using Morris water-maze (MWM) test. TNF-α and IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, along with NF-κB activity determined by ELISA. The morphology of hippocampal tissues were further observed by HE staining. Learning and memory abilities of mice were significantly impaired at day 10 and day 14 post-surgery, as partial hepatectomy significantly prolonged the escape latency, decreased time at the original platform quadrant and frequency of crossing in group P when compared to group C (p < 0.05). The surgery also increased the contents of TNF-α, IL-1β, and NF-κB activity at all time points after surgery (p < 0.05). The introduction of hydrogen-rich saline (group PH) partially rescued spatial memory and learning as it shortened escape latency and increased time and crossing frequency of original platform compared to group P (p < 0.05). Moreover, such treatment also decreased TNF-α and IL-1β levels and NF-κB activity (p < 0.05). In addition, cell necrosis in the hippocampus induced by hepatectomy was also rescued by hydrogen-rich saline. Hydrogen-rich saline can alleviate POCD via inhibiting NF-κB activity in the hippocampus and reducing inflammatory response.

Mitigating ER stress and oxidative stress is beneficial after traumatic brain injury

Event Abstract Back to Event Mitigating ER stress and oxidative stress is beneficial after traumatic brain injury Raghu Vemuganti1*, S L. Mehta1, L Bodden1, V Nakka1, T H. Kim1, R Chandran1, E Udho2, P Cengiz2 and R J. Dempsey1 1 University of Wisconsin, Department of Neurological Surgery, United States 2 University of Wisconsin, Department of Pediatrics, United States Endoplasmic reticulum (ER) stress and oxidative stress are known proponents of secondary neuronal damage and neurological dysfunction following traumatic brain injury (TBI). A moderate controlled cortical impact-induced TBI in adult mice significantly induced the phosphorylation of PERK and eIF2α and also increased the expression of the down-stream CHOP and ATF4 indicating activation of PERK signaling pathway that kills neurons if uncontrolled. We further show that treating adult mice with salubrinal (an inhibitor of PERK pathway) leads to a significant decrease in the secondary cortical contusion with a good window of efficacy (5 min to 4h after injury). In the cohort of mice treated with salubrinal at 2h after TBI, there was a significant improvement in the motor function recovery measured by rotarod test and beam walk test. TBI also increased the expression NADPH oxidase subunit NOX2 (gp91phox; promotes formation of reactive oxygen species) and the transcription factor Nrf2 (induces down-stream anti-oxidant enzymes). We tested apocynin (an inhibitor of NOX2; 10 mg/Kg) and TBHQ (an activator of Nrf2; 25 mg/Kg) alone or in combination in cohorts of mice subjected to CCI injury. Either apocynin or TBHQ treatment alone significantly improved the motor function after TBI compared to vehicle control. The drug treated mice stayed longer on rotarod and made fewer foot faults in beam walk test between day 1 to 7 after injury. The combination therapy (apocynin + TBHQ) also significantly improved the post-TBI motor function compared to vehicle control, but there was no additive effect of the 2 drugs. Following the combination therapy, mice spent significantly greater time with higher frequency in the platform quadrant as compared to vehicle control when tested for cognition by Morris Water maze test at 3 weeks after injury. The cortical contusion volume was also significantly lower in the combo therapy group compared to vehicle control. In conclusion, these studies show that controlling either ER stress or oxidative stress significantly improves the functional outcome and tissue sparing after TBI. Keywords: Endoplasmic Reticulum Stress, Oxidative Stress, Motor function, in vivo, Brain Injury Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Free Paper Session 2: Molecular Mechanisms of the Nervous System Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Vemuganti R, Mehta SL, Bodden L, Nakka V, Kim TH, Chandran R, Udho E, Cengiz P and Dempsey RJ (2016). Mitigating ER stress and oxidative stress is beneficial after traumatic brain injury. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00105 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Prof. Raghu Vemuganti, University of Wisconsin, Department of Neurological Surgery, Madison, WI, United States, vemuganti@neurosurgery.wisc.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Raghu Vemuganti S L Mehta L Bodden V Nakka T H Kim R Chandran E Udho P Cengiz R J Dempsey Google Raghu Vemuganti S L Mehta L Bodden V Nakka T H Kim R Chandran E Udho P Cengiz R J Dempsey Google Scholar Raghu Vemuganti S L Mehta L Bodden V Nakka T H Kim R Chandran E Udho P Cengiz R J Dempsey PubMed Raghu Vemuganti S L Mehta L Bodden V Nakka T H Kim R Chandran E Udho P Cengiz R J Dempsey Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Neuroprotective effects of ginseng protein on PI3K/Akt signaling pathway in the hippocampus of D-galactose/AlCl3 inducing rats model of Alzheimer’s disease

Ethnopharmacological relevanceAlzheimer disease (AD) is a progressive neurodegenerative disease, with progressive memory loss, cognitive deterioration, and behavioral disorders. Ginseng (Panax ginseng C.A. Meyer) is widely used in China to treat various kinds of nervous system disorders. The study aimed to explore the therapeutic effect of ginseng protein (GP) on Alzheimer’s disease and its correlation with the PI3K/Akt signaling pathway to understand the mechanism underlying the neuroprotective effect of ginseng. Material and methodsThe AD rat model was established by intraperitoneally injecting D-galactose [60mg/(kgd)] followed by intragastrically administering AlCl3 [40mg/(kgd)] for 90 days. From day 60, the GP groups were intragastrically administered with GP 0.05 or 0.1g/kg twice daily for 30 days. The ethology of rats was tested by Morris water maze test. The content of Aβ1-42 and p-tau in the hippocampus of rats was detected by enzyme-linked immunosorbent assay. The expression of mRNAs and proteins of PI3K, Akt, phosphorylated Akt (p-Akt), Bcl-2, and Bax in the hippocampus was detected by real-time quantitative reverse transcription polymerase chain reaction and Western blot assay. ResultsGP was found to significantly improve the memory ability of AD rats and prolong the times of crossing the platform and the percentage of residence time in the original platform quadrant of spatial probe test. GP also reduced the content of Aβ1-42 and p-tau and improved the mRNA and protein expression of PI3K, p-Akt/Akt, and Bcl-2/Bax in the hippocampus. ConclusionsGP could improve the memory ability and reduce the content of Aβ1-42 and p-tau in AD rats. The anti-AD effects of GP were in part mediated by PI3K/Akt signaling pathway activation.

Effect of melatonin on postoperative apoptosis in hippocampal cells of aged rats undergoing isoflurane anesthesia

Objective To evaluate the effect of melatonin on postoperative apoptosis in hippocampal cells of aged rats undergoing surgery under isoflurane anesthesia. Methods Sixty healthy male Sprague-Dawley rats, aged 18 months, weighing 550–610 g, were randomized into 5 groups(n=12 each)using a random number table: control group(group C), 2% isoflurane anesthesia group(group I), 2% isoflurane + melatonin group(group IM), surgery group(group S), and surgery + melatonin group(group SM). Group IM inhaled 2% isoflurane for 4 h. Group S inhaled 2% isoflurane for 4 h, and then back surgery was performed.In IM and SM groups, melatonin 10 mg/kg was injected intraperitoneally everyday for 7 consecutive days before anesthesia, while the equal volume of normal saline was given in C, I and S groups.The cognitive function was assessed using the Morris water maze test on 2nd after anesthesia.The escape latency, space exploration time spent at the original platform quadrant, and frequency of crossing the original platform were recorded.After the end of the Morris water maze test, the rats were sacrificed on that day, and the hippocampi were isolated for detection of the expression of Bcl-2, Bax and caspase-3 by Western blot.Bcl-2/Bax ratio was calculated. Results Compared with group C, the escape latency was significantly prolonged on days 1-3 after anesthesia in group I, the escape latency was significantly prolonged, the space exploration time spent at the original platform quadrant was shortened, and the frequency of crossing the original platform was decreased on days 1-3 after operation in group S, and the expression of caspase-3 and Bax was significantly up-regulated, the expression of Bcl-2 was down-regulated, and Bcl-2/Bax ratio was decreased in I and S groups(P 0.05). Compared with group S, the escape latency was significantly shortened, the space exploration time spent at the original platform quadrant was prolonged, and the frequency of crossing the original platform was increased on days 3-5 after operation, the expression of caspase-3 and Bax was significantly down-regulated, the expression of Bcl-2 was up-regulated, and Bcl-2/Bax ratio was increased in group SM(P<0.05). Conclusion Melatonin can inhibit apoptosis in hippocampal cells and improve postoperative cognitive dysfunction in aged rats undergoing isoflurane anesthesia. Key words: Melatonin; Isoflurane; Anesthesia; Postoperative complications; Cognition disorders; Apoptosis; Hippocampus