Memory Ability Of Rats Research Articles

Protective role of Dihydromyricetin in Alzheimer's disease rat model associated with activating AMPK/SIRT1 signaling pathway.

The aim of the present study was to understand the possible role of the Dihydromyricetin (DHM) in Alzheimer’s disease (AD) rat model through regulation of the AMPK/SIRT1 signaling pathway. Rats were divided into Sham group, AD group, AD + DHM (100 mg/kg) group and AD + DHM (200 mg/kg) group. The spatial learning and memory abilities of rats were assessed by Morris Water Maze. Then, the inflammatory cytokines expressions were determined by radioimmunoassay while expressions of AMPK/SIRT1 pathway-related proteins by Western blot; and the apoptosis of hippocampal cells was detected by TdT-mediated dUTP nick end labeling assay. AD rats had an extended escape latency with decreases in the number of platform crossings, the target quadrant residence time, as well as swimming speed, and the inflammatory cytokines in serum and hippocampus were significantly elevated but AMPK/SIRT1 pathway-related proteins were reduced. Meanwhile, the apoptosis of hippocampal cells was significantly up-regulated with decreased Bcl-2 and increased Bax, as compared with Sham rats (all P<0.05). After AD rats treated with 100 or 200 mg/kg of DHM, the above effects were significantly reversed, resulting in a completely opposite tendency, and especially with 200 mg/kg DHM treatment, the improvement of AD rats was more obvious. DHM exerts protective role in AD via up-regulation of AMPK/SIRT1 pathway to inhibit inflammatory responses and hippocampal cell apoptosis and ameliorate cognitive function.

Effects of aminooxyacetic acid on hippocampal mitochondria in rats with chronic alcoholism: the analysis of learning and memory-related genes

The incidence of chronic alcoholism leading to central and peripheral nervous system damage has been increasing year-to-year. The purpose of this study is to explore the effects of aminooxyacetic acid on hippocampus mitochondria in rats with chronic alcoholism and analyze learning and memory-related genes. Sixty male Sprague Dawley rats were randomly divided into three groups. Except for the control group, each group was fed with the water containing (v/v) 6% alcohol for 28 days. After 14 days, rats in the treatment group were intraperitoneally injected daily for 14 days with aminooxyacetic acid. High throughput sequencing was combined and tested for learning and memory abilities, Hydrogen sulfide content, catalase activity in mitochondria, and the expression of F-actin in the hippocampus of the rats in each group. Compared with the control group, the learning and memory abilities of rats with chronic alcoholism were significantly impaired, mitochondria contained vacuoles, hydrogen sulfide increased, but catalase activity and F-actin content were significantly decreased, After treatment with aminooxyacetic acid, mitochondrial morphology improved, hydrogen sulfide content was decreased, while catalase activity and F-actin expression of in hippocampus were increased. This indicates that aminooxyacetic acid may improve learning and memory in rats with chronic alcoholism, and the mechanism is related to decreased hydrogen sulfide content and an increase of both catalase activity and F-actin level in the hippocampus, thereby reducing the damage of alcohol to mitochondria and neurons.

Dopamine in the hippocampal dentate gyrus modulates spatial learning via D1-like receptors

Increasing evidence supports that dopamine (DA) plays an important role in the hippocampal function via activation of D1-like receptors (D1Rs). As the entry structure of the hippocampal formation, the hippocampal dentate gyrus (DG) is critically involved in spatial learning and memory. Despite a number of studies investigated how DA influences CA1 plasticity and learning, there are fewer studies examining the influence of DA signaling to the DG. To investigate the roles of DA and D1Rs of the DG in modulation of spatial learning and memory, the spatial learning and memory abilities of rats were measured by Morris water maze (MWM), and then the concentration of DA in the DG region was determined by in vivo brain microdialysis and HPLC. Next, the effects of local microinjection of SCH23390 (an antagonist of D1Rs) on extracellular levels of excitatory amino acids (EAAs), including glutamate (Glu) and aspartate (Asp), were measured in the DG region during MWM test in freely-moving conscious rats. During the place navigation trial of MWM test, the escape latency was decreased with the increase in training days, and DA concentration in the DG was significantly increased. In SCH23390 group rats, the escape latency was increased in place navigation trial and the percentage of time spent in target quadrant and the number of platform crossings were decreased in spatial probe trial during MWM test, compared with vehicle group. Furthermore, in vehicle group rats, the extracellular levels of Glu and Asp in the DG were significantly increased during place navigation trial of MWM test, and these responses were partly inhibited by microinjection of SCH23390. Our results suggest that DA activation of D1Rs in the hippocampal DG promotes spatial learning and memory, in part by modulating the responses of EAAs during spatial learning.

Down-Regulation of Mir-145 Improves Learning and Memory Abilities in Epileptic Rats by Regulating Hippocampal Neuron Apoptosis

To investigate effect of miR-145 on learning and memory ability in rats with epilepsy. Rats with epilepsy were induced by lithium chloride-pilocarpine. miR-145 antagomir and antagomir-control were injected into epileptic brains by the stereotactic technique, respectively. Then, rats were divided into a normal group (N), epilepsy group (Ep), miR-145 antagomir group (A) and antagomir-control group (C). After 1 and 7 days of treatment, the expression of miR-145 and Caspase-9 were detected, and the apoptosis of hippocampal neurons in CA1 of hippocampus was detected. After 7 days of treatment, the learning and memory abilities of rats was measured by using the Morris water maze test. The rat epilepsy model was successfully constructed. Compared with the N group, the target quadrant time and platform crossing times were reduced and the expression of miR-145 and Caspase-9 was increased in the epilepsy groups (P < 0.05). Compared with the Ep and C groups, the target quadrant time and platform crossing times were increased and the expression of miR-145 and Caspase-9 was down-regulated in the A group (P < 0.05). The number of apoptotic hippocampal neurons in the hippocampal CAl area of the Ep group was more than that in the N group and in the A group was less than that in the C group at 1 and 7 days after modeling respectively (P < 0.05). Down-regulated miR-145 improved the apoptosis of hippocampal neurons by reducing the Caspase-9 expression in hippocampus and further affected learning and memory abilities of rats with epilepsy.

The effect of different frequencies of electroacupuncture on BDNF and NGF expression in the hippocampal CA3 area of the ischemic hemisphere in cerebral ischemic rats.

ObjectiveThe aim of this study was to observe the effects of different frequencies of electroacupuncture (EA) on expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampal CA3 region of cerebral ischemic rats.MethodsMiddle cerebral artery occlusion was successfully introduced to simulate cerebral infarction in 48 healthy male Sprague–Dawley rats. Totally, 48 rats were randomly divided into three groups: the control group, the EA 5-Hz group, and the EA 50-Hz group, 16 in each group. The rats in the control group were placed in an ordinary cage and fed normally without any treatment. EA treatment was given at a certain frequency 24 hours after surgery in the EA 5-Hz group and EA 50-Hz group. Morris water maze test was used to measure the learning and memory abilities of rats in each group after 14-day treatment with EA. Immunohistochemical staining was used to detect the expression of BDNF- and NGF-positive cells in the ischemic hippocampal CA3 area of the rats.ResultsThe EA 5-Hz group and EA 50-Hz group had significantly improved learning and memory ability compared with the control group according to Morris water maze findings (P<0.05). The number of BDNF- and NGF-positive cells in the hippocampal CA3 region of the ischemic hemisphere in the 5-Hz group and 50-Hz EA group was significantly more than that in the control group after EA treatment (P<0.05), and the difference in the 50-Hz group was more obvious than that in the 5-Hz group. The difference was statistically significant (P<0.05).ConclusionEA stimulation of “Baihui” and “Dazhui” can promote the expression of BDNF and NGF in the hippocampal CA3 region of cerebral ischemic rats, and the 50-Hz EA stimulation effect is more obvious.

Effect of electroacupuncture on learning and memory in rats with cerebral ischemia-reperfusion and its mechanism

Objective To explore the effect and possible mechanism of electroacupuncture on learning and memory impairment in rats with cerebral ischemia reperfusion. Methods 90 SD rats used for step-down test were divided into normal control group, simple cerebral ischemia reperfusion of 7 d, 14 d, 30 d, 60 d group (I/R) and cerebral ischemia reperfusion of 7 d, 14 d, 30 d, 60 d and electroacupuncture intervention group (I/R+ EA), through simple random sampling method (10 rats in each group); 70 SD rats used for molecular biology experiments were randomly divided into normal control group, simple cerebral ischemia and reperfusion of 3 h, 6 h, 12 h group (I/R) and cerebral ischemia reperfusion of 3 h, 6 h, 12 h and electroacupuncture intervention group (I/R+ EA), n=10.Use suture method to make model of cerebral ischemia reperfusion in rats.Take the rats' baihui acupoint and shuigou acupoint to acupuncture.The final strength was 5 mA and the duration was 30 minutes.Step down test was used to observe the restoration of learning and memory in rats.Western blot was used to detect the expression of procaspase-3, procaspase-12, PARP and ICAD in rat cerebral cortex and striatum.Immunofluorescence histochemical method was used to detect the number of GRP94 positive cells. Results The results of the platform showed that the learning and memory abilities of the rats were obviously improved after electroacupuncture treatment.Electric shock incubation period of rats in electroacupuncture of 7 d and 14 d group was (90.60±17.01) and (128.80±8.85) respectively.It was significantly higher than that of cerebral ischemia reperfusion of 7 d group(51.20±5.09) and 14 d group(105.00±10.39). The number of mistakes in single foot jump of rats in electroacupuncture of 7 d and 14 d group was (3.90±0.99) and (2.70±0.67) respectively.It was significantly lower than that of 7 d group(9.20±1.61) and 14 d group(6.10±0.99). Through SPSS13.0 statistical software one-way ANOVA, the difference was statistically significant (P<0.05). Western blot results showed that the expression of procaspase-3, procaspase-12, PARP protein precursor and ICAD protein, upregulation increased after electroacupuncture(P<0.05). The results of immunofluorescence histochemistry showed that the number of positive cells of GRP94 protein was significantly decreased after 3 h, 6 h and 12 h after electroacupuncture intervention compared with the corresponding I/R group. Conclusion Electroacupuncture can effectively improve the learning and memory ability of rats with ischemia-reperfusion, which may be related to the apoptosis of cerebral cells after cerebral ischemia reperfusion injury by blocking the apoptosis pathway mediated by endoplasmic reticulum and inflammatory factors. Key words: Electroacupuncture; Cerebral ischemia reperfusion; Apoptosis; Learning and memory; Rat

Research on the changes in balance motion behavior and learning, as well as memory abilities of rats with multiple cerebral concussion-induced chronic traumatic encephalopathy and the underlying mechanism.

To study the effects of multiple cerebral concussion (MCC)-induced chronic traumatic encephalopathy on balance motion behavior learning and memory abilities of rats and its possible mechanism. 4MCC rat models were established by means of striking the head (4MCC group, n=15), while normal Sprague-Dawley (SD) rats were used as controls (C group, n=15). At 2 weeks after injury, balance beam (BB) test, beam walking (BW) test and Morris water maze (MWM) test were performed, respectively. The metabolites in brain tissues of rats, the number of glial fibrillary acidic protein (GFAP)-positive cells and apoptotic cells in brain slices of rats, and the expression levels of phosphorylated tau (p-tau) and Aβ1-40 proteins were detected. The score of rats in 4MCC group was significantly lower than that in C group (p<0.01). The escape latencies of rats in 4MCC group on the 4th-7th days during training and the time reaching the platform were significantly longer (p<0.05), but the residence time in the target quadrant was obviously shorter (p<0.01). Naphthalene acetic acid (NAA) and creatinine (Cr) values in septal coronal section in 4MCC group were significantly lower, but choline (Cho) and myo-inositol (MI) values were obviously higher (p<0.01). The number of GFAP-positive cells in the hippocampal and septal areas in 4MCC group were significantly larger (p<0.01). In the hippocampal and septal areas of 4MCC group, the number of apoptotic cells was obviously larger (p<0.01), and the expression levels of p-tau and Aβ1-40 proteins were significantly higher (p<0.01). Thus, MCC-induced chronic traumatic encephalopathy can increase the expressions of p-tau and Aβ1-40 proteins in the hippocampal and septal areas, leading to damage of hippocampal and septal neurons and increasing the number of astrocytes in the hippocampal and septal areas, ultimately damaging the balance motion behavior and learning, as well as memory abilities of rats.

The influence of high-intensity interval training on spatial memory ability in rats

High-intensity interval training (HIIT) has been shown to enhance the expression of brain-derived neurotrophic factor. This study was aimed to clarify the influence of HIIT on spatial memory ability. Eighteen male Sprague–Dawley rats were used in this study, and 9 rats were kept in a breeding room for 2 months (control). Remaining 9 rats were forced to run on a treadmill at a speed corresponding to 80% of the maximal speed for 2 min and then at a speed equal to 50% of its maximum for 3 min (HIIT). These trials repeated three consecutive times. HIIT performed three times a week for 2 months. After HIIT, a treadmill endurance test, which rats forced to run on the treadmill with a stepwise increase of speed, was conducted. Spatial memory ability for each rat was estimated using Morris water maze test, which were determined from the time to reach the hidden goal stage in the circular pool. Morris water maze test were conducted 4 times per a day for 4 days. After these tests, extensor digitorum longus muscle and soleus muscle were isolated, and weight per body weight (MW/BW) of each muscle was measured. No significant improvement was revealed in time for reaching goal using Morris water maze test between the control group and the HIIT group. Running time evaluated by a treadmill endurance test was significantly longer in the HIIT group ( P < 0.05). Significant increases were not detected in the MW/BW of extensor digitorum longus muscle by HIIT. The MW/BW of soleus muscle was significantly heavier in the HIIT group compared to the control group ( P < 0.05). This study revealed that HIIT improved endurance capacity and increased soleus muscle weight per body weight, however, significant improvement of spatial memory ability could not be found out.

Electroacupuncture Ameliorates Cognitive Impairment and Spontaneous Low-Frequency Brain Activity in Rats with Ischemic Stroke

To evaluate whether electroacupuncture (EA) at Baihui (DU20) and Shenting (DU24) acupoints could improve cognitive function and enhance spontaneous low-frequency brain activity in rats with ischemic stroke. Total 36 rats were randomly divided into 3 groups-the sham surgery (Sham) group, the middle cerebral artery occlusion induced cognitive deficit (MICD) group, and the MICD with EA (MICD + EA) treatment group. The rats in MICD + EA group received EA treatment at DU20 and DU24 acupoints for 14 consecutive days after the surgery. The Morris water maze test was performed to assess the spatial learning and memory ability of the rats. Magnetic resonance imaging (MRI) was used to investigate the infarction volume and spontaneous low-frequency brain activity of each group. After EA for 14 days, the learning and memory ability of the MICD rats was improved, and the brain infarction volume was reduced. Furthermore, basing on the fMRI amplitude of low-frequency fluctuation (ALFF) analysis, the decreased ALFF of the MICD rats was found in auditory cortex, cingulate gyrus, lateral nucleus group of dorsal thalamus, hippocampus, motor cortex, prelimbic cortex, retrosplenial cortex, and sensory cortex compared with the rats in sham group. However, these suppressive regions were notably attenuated after EA treatment. Our results suggested that EA at DU20 and DU24 acupoints could ameliorate cognitive impairment in rats with ischemic stroke, and the protective effect of EA may attribute to reactivating the cognition-related brain regions, such as hippocampus, retrosplenial cortex, cingulate gyrus, prelimbic cortex, and sensory cortex.

The protective effect of hydrogen-rich water on irradiation-induced cognitive dysfunction

Objective To investigate the protective effect of hydrogen-rich water on rat cognitive dysfunction induced by ionizing radiation. Methods A total of 20 SD rats were randomly divided into four groups with the ramdom number table method: control group (C), hydrogen-rich water group (HRW), irradiation group (IR) and hydrogen-rich water intervention group (HRW+ IR), with 5 rats in each group. The spatial memory ability of rats was tested by a morris water maze. The expression of apoptosis-related genes was detected by real-time fluorescence quantitative PCR. The changes of glutathione (GSH), 8-hydroxydeoxy guanosine (8-OHdG) and malondialdehyde (MDA) and SOD were also measured. Results The escape latency (F=6.003, P<0.05) and the swimming distances (F=3.850, P<0.05) of rats in four different groups had statistically significant differences. Compared with the IR group, the escape latency of the HRW+ IR group was significantly decreased at 3, 4, 5 d after irradiation (P<0.05), and the swimming distance of this group became much longer (P<0.05). The levels of GSH, 8-OHdG and MDA in these four groups had statistically significant differences (F=6.450, 5.033, 4.113, P<0.05). Compared with IR group, the concentration of GSH was increased (P<0.05), but MDA and 8-OHdG decreased (P<0.05) in the brain tissue of HRW+ IR group, and the expressions of caspase-3, caspase-9 and bax genes were reduced (t=2.956, 3.087, 5.246, P<0.05), while the expression of bcl-2 gene was enhanced (t=-3.640, P<0.05) in the HRW+ IR group. Conclusions Hydrogen-rich water attenuates the oxidative damage of ionizing radiation by neutralizing oxyhydrogen free radicals and thus protects brain from radiation damage. Key words: Hydrogen-rich water; Ionizing radiation; Cognitive dysfunction; Radiation protection

Postconditioning with sevoflurane ameliorates spatial learning and memory deficit via attenuating endoplasmic reticulum stress induced neuron apoptosis in a rat model of hemorrhage shock and resuscitation

Hemorrhage shock could initiate endoplasmic reticulum stress (ERS) and then induce neuronal apoptosis. The aim of this study was to investigate whether sevoflurane postconditioning could attenuate brain injury via suppressing apoptosis induced by ERS. Seventy male rats were randomized into five groups: sham, shock, low concentration (sevo1, 1.2%), middle concentration (sevo2, 2.4%) and high concentration (sevo3, 3.6%) of sevoflurane postconditioning. Hemorrhage shock was induced by removing 40% of the total blood volume during an interval of 30 min. 1 h after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The spatial learning and memory ability of rats were measured by Morris water maze (MWM) test three days after the operation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region were assessed after the MWM test. The expression of C/EBP-homologousprotein (CHOP) and glucose-regulated protein 78 (GRP78) in the hippocampus were measured at 24 h after reperfusion. We found that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning and memory ability, decreased the TUNEL-positive cells, and reduced the GRP78 and CHOP expression compared with the shock group. These results suggested that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% could ameliorate spatial learning and memory deficit after hemorrhage shock and resuscitation injury via suppressing apoptosis induced by ERS.

Blue light filtered white light induces depression-like responses and temporary spatial learning deficits in rats.

Ambient light has a vital impact on mood and cognitive functions. Blue light has been previously reported to play a salient role in the antidepressant effect via melanopsin. Whether blue light filtered white light (BFW) affects mood and cognitive functions remains unclear. The present study aimed to investigate whether BFW led to depression-like symptoms and cognitive deficits including spatial learning and memory abilities in rats, and whether they were associated with the light-responsive function in retinal explants. Male Sprague-Dawley albino rats were randomly divided into 2 groups (n = 10) and treated with a white light-emitting diode (LED) light source and BFW light source, respectively, under a standard 12 : 12 h L/D condition over 30 days. The sucrose consumption test, forced swim test (FST) and the level of plasma corticosterone (CORT) were employed to evaluate depression-like symptoms in rats. Cognitive functions were assessed by the Morris water maze (MWM) test. A multi-electrode array (MEA) system was utilized to measure electro-retinogram (ERG) responses induced by white or BFW flashes. The effect of BFW over 30 days on depression-like responses in rats was indicated by decreased sucrose consumption in the sucrose consumption test, an increased immobility time in the FST and an elevated level of plasma CORT. BFW led to temporary spatial learning deficits in rats, which was evidenced by prolonged escape latency and swimming distances in the spatial navigation test. However, no changes were observed in the short memory ability of rats treated with BFW. The micro-ERG results showed a delayed implicit time and reduced amplitudes evoked by BFW flashes compared to the white flash group. BFW induces depression-like symptoms and temporary spatial learning deficits in rats, which might be closely related to the impairment of light-evoked output signals in the retina.

Exposure to intermittent hypoxia impairs learning and memory ability in rats

To study the effects of chronic intermittent hypoxia (CIH) on learning and memory ability in Sprague–Dawley rats, we established a rat model of CIH. A total of 24 male Sprague–Dawley rats were included and were assigned to three experimental groups (n = 8/group): the unhandled control (UC) group (normal feeding for 4 weeks), the CIH group (CIH for 4 weeks), and the removal of hypoxia (RH) group (normal feeding for 4 weeks after CIH for 4 weeks). All the results were analyzed using one-way ANOVA and comparison between groups was performed using S–N–K method. Performance on the Morris water maze test (a learning and memory test) was significantly worse for CIH rats than for UC rats and RH rats (P < 0.05), but was significantly better for RH rats than for UC rats (P < 0.05). Synaptophysin expression in the CA3 region of the hippocampus was reduced in the CIH group and the RH group compared with the UC group (P < 0.05), but was significantly greater in the RH group than in the CIH group (P < 0.05). Synaptophysin is a calcium-binding protein located in the membranes of presynaptic vesicles. Changes of synaptophysin expression may indirectly reflect the structural changes in the hippocampal CA3 region. In rats, CIH can cause declines in learning ability and memory and reduce the expression of synaptophysin in the CA3 region of the hippocampus; these effects could be partially rescued by the removal of hypoxic factors. The observed decline in learning and memory ability in rats may relate to a decrease in synapse quantity and structural changes in the CA3 region of the hippocampus.

MiR-138/SIRT1 axis is implicated in impaired learning and memory abilities of cerebral ischemia/reperfusion injured rats

The present study aimed to explore whether deregulated miR-138 is implicated in cerebral I/R injury-impaired learning and memory abilities. Rats were subjected to bilateral common carotid occlusion followed by reperfusion to induce cerebral I/R injury. A model of oxygen-glucose deprivation and reperfusion (OGD/R) was conducted to mimic cerebral I/R conditions in vitro. MiR-138 expression levels were reduced in the hippocampus of cerebral I/R injured rats. Inhibition of miR-138 ameliorated the impaired learning and memory abilities of rats, and promoted autophagy and thus attenuated apoptosis in the OGD/R-treated hippocampal neurons. Moreover, miR-138 targets the 3′-UTR of SIRT1 and repressed its expression. These results showed that miR-138 could improve the learning and memory abilities via promoting autophagy under cerebral I/R injured conditions.

Neuroprotective effect of docosahexaenoic acid in rat traumatic brain injury model via regulation of TLR4/NF-Kappa B signaling pathway.

The experiments were conducted to prove that docosahexaenoic acid (DHA) alleviates traumatic brain injury (TBI) through regulating TLR4/NF-Kappa B signaling pathway. Bioinformatic analysis was performed using published data from Gene Expression Omnibus (GEO) database to investigate differentially expressed genes and signaling pathways. Controlled cortical impact (CCI) injury rat model was built, and DHA (16 mg/kg in DMSO, once each day) was used to treat TBI rats. Neurological severity score (NSS) and beam walking test and rotarod test were used to confirm whether DHA is neuron-protective against TBI. The expression of TLR4, NF-Kappa B p65, (TNF)-α and IL-1β were examined by qRT-PCR and western blot. The impact of DHA on neurocyte apoptosis was validated by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. The influence of DHA on CD11b and GFAP expression in the hippocampus was determined through immunohistochemical analysis. TLR4/NF Kappa B pathway was suggested to be closely correlated with TBI by bioinformatic analysis. DHA could improve the neurological function and learning and memory ability of rats after TBI as well as promote neurocytes from apoptosis. TLR4 expression and the expression of inflammatory mediator NF-Kappa B were also repressed by DHA treatment. DHA exerted a neuron-protective influence in a rat model of TBI via repressing TLR4/NF-Kappa B pathway.

Atorvastatin Attenuates Cognitive Deficits and Neuroinflammation Induced by Aβ1-42 Involving Modulation of TLR4/TRAF6/NF-κB Pathway.

Inflammatory damage aggravates the progression of Alzheimer's disease (AD) and the mechanism of inflammatory damage may provide a new therapeutic window for the treatment of AD. Toll-like receptor 4 (TLR4)-mediated signaling can regulate the inflammatory process. However, changes in TLR4 signaling pathway induced by beta-amyloid (Aβ) have not been well characterized in brain, especially in the hippocampus. In the present study, we explored the changes of TLR4 signaling pathway induced by Aβ in the hippocampus and the role of atorvastatin in modulating this signal pathway and neurotoxicity induced by Aβ. Experimental AD rats were induced by intrahippocampal injection of Aβ1-42, and the rats were treated with atorvastatin by oral gavage from 3weeks before to 6days after injections of Aβ1-42. To determine the spatial learning and memory ability of rats in the AD models, Morris water maze (MWM) was performed. The expression of the glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule-1 (Iba-1), TLR4, tumor necrosis factor receptor-associated factor 6 (TRAF6), and nuclear transcription factor (NF)-κB (NF-κB) protein in the hippocampus was detected by immunohistochemistry and Western blot. Compared to the control group, increased expression of TLR4, TRAF6, and NF-κB was observed in the hippocampus at 7days post-injection of Aβ (P < 0.01). Furthermore, atorvastatin treatment significantly ameliorated cognitive deficits of rats, attenuated microglia and astrocyte activation, inhibited apoptosis, and down-regulated the expression of TLR4, TRAF6, and NF-κB, both at the mRNA and protein levels (P < 0.01). TLR4 signaling pathway is thus actively involved in Aβ-induced neuroinflammation and atorvastatin treatment can exert the therapeutic benefits for AD via the TLR4 signaling pathway.

Lanthanum chloride impairs memory in rats by disturbing the glutamate-glutamine cycle and over-activating NMDA receptors

Studies have reported that lanthanum chloride (LaCl3) can across the blood-brain barrier, accumulate in the brain and affect the spatial learning and memory abilities. However, the potential mechanism that LaCl3-induced neurotoxic effects has not yet been defined. Glutamate (Glu) is a vital excitatory neurotransmitter, and the excessive Glu accumulation in extracellular space can induce excitatory neurotoxicity. This study was designed to research the influence of LaCl3 on the spatial learning and memory abilities of rats and to discuss the possible mechanism underlying this effect regarding the extracellular Glu concentration, the Glu-glutamine (Gln) cycle and the N-methyl-D-aspartate (NMDA) receptors. Four groups of Wistar rats were exposed to 0%, 0.125%, 0.25% or 0.5% LaCl3 via the drinking water from the day of conception to 1 month after weaning. These results showed that LaCl3 exposure damaged spatial learning and memory, long-term potentiation, and neuronal ultrastructure, generated an excessive accumulation of glutamate, significantly decreased the expression of glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), glutamine synthetase (GS) and phosphate-activated glutaminase (PAG), and increased the expression of GluN1, GluN2A and GluN2B. This study showed that LaCl3 impaired the rats' spatial learning and memory abilities by disturbing the Glu-Gln cycle and over-activating NMDA receptors thereby inducing excitotoxicity.

Neuroprotective effects of hyperbaric oxygen therapy in combination with Schwann cell transplantation in hippocampal fimbria transected rats

BackgroundAlzheimer's disease (AD) is usually characterized by cognitive impairments, and the treatment is currently far from satisfaction. Hyperbaric oxygen (HBO) therapy or Schwann cell (SC) transplantation has shown partial effects on the treatment of AD. However, their combined effects and underlying mechanisms remain unknown.MethodsAD rat model was induced by cutting off the hippocampal fimbria under stereotaxic apparatus. Animals were then randomly divided into five groups: sham, AD with no treatment (AD), AD receiving HBO therapy (AD+HBO), AD with SC transplantation (AD+SC), and AD receiving HBO combining with SC transplantation (AD+SC+HBO). Morris Water Maze was used to test the learning and memory ability of rats. Real‐time polymerase chain reaction (RT‐PCR), Immunohistochemistry, western blot were used to evaluate the expression of neurotrophin factors and related signal molecules.ResultsAD model was established successfully. Combining HBO therapy with SC transplantation had better effects on AD rats than SC transplantation or HBO therapy alone, not only in the enhancement of learning and memory recovery but also in the increased expression of B‐cell lymphoma‐extra large (Bcl‐xl).ConclusionCombining SC transplantation with HBO therapy has a prospective therapeutic potential for the further treatment of AD. The possible mechanism could be linked to the up‐regulation of Bcl‐xl gene.

Effects of Acupuncture at "Shenmen" (HT 7) on Brainwaves and Cognitive Ability in Rats with Sleep Deprivation

To observe the effects of acupuncture at "Shenmen" (HT 7) on brainwaves and cognitive ability in rats with sleep deprivation. SD rats were randomly divided into control group, model group, acupuncture group and sham acupuncture group, 15 rats in each group. Insomnia model rats were established by sleep deprivation for 72 hours. Acupuncture was applied to acupuncture group at bilateral "Shenmen" (HT 7) for 20 min, once daily for 7 days. Rats in the sham acupuncture group received superficial insertion of 1 mm and without retaining needle. The learning and memory abilities of rats were eva-luated by Hexagonal maze. The BL-420 F physiological recorder was used to record EEG for 30 min on the 1st, 4th, 7th and 10th day respectively, and the frequency of each wave was analyzed. After sleep deprivation, the frequency of searching the exits of Hexagonal maze in the model group was obviously increased, the searching time was shortened, the number of searching errors was increased obviously, and the cognitive rate was decreased (P<0.01). Compared with the model group and the sham acupuncture group, the frequency of searching the exits in the acupuncture group was obviously decreased, the searching time was longer, the number of seeking errors was decreased, and the cognitive rate was increased (P<0.05). Compared with the control group, the EEG of δ wave in the model group was decreased while β wave increased with statistical significance (P<0.01). Compared with the model group, the δ wave of rats in the acupuncture group was significantly increased and the β wave was significantly decreased (P<0.05). There were no statistically significant differences between the sham acupuncture group and the model group (P>0.05). Acupuncture at HT 7 can effectively improve the cognitive abilities and brainwaves in sleep deprived rats.

Pretreatment with minocycline improves neurogenesis and behavior performance after midazolam exposure in neonatal rats.

Laboratory studies suggested that general anesthetics induce neuroapoptosis and inhibit neurogenesis in developing brains of animals. Minocycline exerts neuroprotection against a wide range of toxic insults in neurodegenerative diseases models. Here, we investigate whether minocycline can alleviate neurogenetic damage and improve cognition following midazolam exposure in neonatal rats. Postnatal 7 days rats were divided randomly into three groups: control group (C), midazolam group (M), and minocycline pretreatment group (MP). After exposure to midazolam, the cell proliferation in the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampus in pups was analyzed by bromodeoxyuridine immunochemistry at 7 days after the administration of anesthesia. Cognitive function was assessed using the Morris water-maze test at 35 days after midazolam exposure. Compared with the control, midazolam reduced cell proliferation both in the SVZ and in the SGZ of the hippocampus of neonatal rats, and decreased spatial learning and memory ability of rats in adulthood significantly. Pretreatment with minocycline increased cell proliferation both in the SVZ and in the SGZ of the hippocampus and improved spatial learning and memory ability compared with midazolam, but it did not mitigate the changes to the normal levels compared with the controls. Our results indicated that pretreatment with minocycline can alleviate midazolam-induced damage in neural stem cell proliferation of neonatal rats and improve spatial learning and memory ability of rats in adulthood.