Spatial Learning In Rats Research Articles

Deep Brain Stimulation Inhibits Epileptic Seizures via Increase of Adenosine Release and Inhibition of ENT1, CD39, and CD73 Expression.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus is an efficacious treatment option for patients with refractory epilepsy. Our previous study demonstrates that adenosine is a potential target of DBS for the treatment of epilepsy. Equilibrative nucleoside transporters-1 (ENT1) and ectonucleotidases (CD39, CD73) function as regulators of extracellular adenosine in the brain. It is unclear whether ENT1, CD39, and CD73 are involved in the mechanism of DBS for epilepsy. A total of 48 SD male rats were divided into four groups: control (naïve rats), Pilo (pilocarpine induced rats with epilepsy), DBS (rats with epilepsy treated with DBS for 8weeks), and sham. In the present study, video electroencephalogram monitoring, Morris water maze assays, in vivo measurements of adenosine using fiber photometry, histochemistry, and western blot were performed on the hippocampus. DBS markedly attenuated spontaneous recurrent seizures (SRSs) and enhanced spatial learning in rats with epilepsy, assessed through video-EEG and water maze assays. Fibred photometry measurements of an adenosine sensor revealed dynamic increase in extracellular adenosine during DBS. The expressions of ENT1, CD39, and CD73 in Pilo group and sham group increased compared with the control group, while the expressions of ENT1, CD39, and CD73 in DBS group decreased compared to that of Pilo group and sham group. The findings indicate that DBS reduces the number of SRSs and improves spatial memory in rats with epilepsy with concomitant decrease of ENT1, CD39, and CD73 expressions. Adenosine-modulating enzymes might be the potential targets of DBS for the treatment of epilepsy.

The novel FAAH inhibitor, MCH1, reduces the infarction area in the motor cortex-related region but does not affect the sensorimotor function or memory and spatial learning in rats exposed to transient middle cerebral artery occlusion

Macamides, amides of fatty acids first isolated from maca (Lepidium meyenii) are potentially responsible for the reduction of ischemic injury in the stroke animal model followed by maca extract administration. This deduction comes from its ability to inhibit the fatty acid amide hydrolase activity, an enzyme related to the endocannabinoid anandamide hydrolysis. However, no study about the effects of isolated macamides on in-vivo models has been published yet. Our objective was to evaluate the effect of a 10-day 30 mg/kg i.p. MCH1 administration, the macamide with the higher FAAH inhibition capability, on the neurological recovery and brain infarction area of Sprague-Dawley rats exposed to the transient middle cerebral artery occlusion (MCAO) model. Our results showed that the group receiving MCH1 for 10 days did not improve Garcia’s neurological score compared to receiving the vehicle only. Likewise, the MCH1 group did not improve their sensorimotor dysfunction as indicated by the latency to detect and remove the tape from the contralateral forepaw in the adhesive removal test, and a similar number of errors with the contralateral forepaw in the foot fault test compared to the vehicle group at the 10th day. Evaluation of the spatial memory and learning using the Barnes test showed longer latency to reach the escape box in the Vehicle and MCH1 groups compared to the control group (no MCAO) only in the retrieval test, while no effect of MCAO procedure or MCH1 administration was observed in the reversal learning test. Despite the lack of behavioral effect of MCH1, analysis of the infarcted areas in the brain using the 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining method in the seven consecutive coronal sections revealed that the infarcted area in the first (bregma + 4.2 mm) and fifth (bregma −3.8 mm) coronal sections of the MCAO + MCH1 group remained similar to the Control group. These results provide evidence that MCH1 can limit damage from ischemic stroke, although it is not reflected in neurological or sensorimotor behavior and spatial learning and memory.

An interventional study of baicalin on neuronal pentraxin-1, neuronal pentraxin-2, and C-reactive protein in Alzheimer's disease rat model.

Baicalin has been shown to promote spatial learning and neural regeneration, which might increase the differentiation of neural stem cells in Alzheimer's disease (AD) rat models. We aimed to study the role of baicalin on neuronal pentraxin-1 (NPTX-1), neuronal pentraxin-2 (NPTX-2), and C-reactive protein (CRP) in AD model rats. The 30 male Sprague Dawley rats were divided into three groups: the control group, the AD model group, and the AD + baicalin group. Then, the Morris water maze was used to verify the effect of baicalin on the memory and spatial learning of rats. Immunohistochemistry and immunofluorescence were used to observe the expression of NPTX-1, NPTX-2, and CRP in brain tissue. Compared with the AD model group, the AD rats treated with baicalin spent significantly less time finding escape latencies (P = 0.008) and had longer cross-platform times in the target quadrant (P = 0.015). In addition, the AD + baicalin group had significantly higher numbers of hippocampal neurons compared with the AD model group (P < 0.05). Baicalin also obviously decreased the apoptosis of neurons. Moreover, compared with the AD model group, the NPTX-1 and CRP expression in the AD + baicalin group was significantly reduced (P = 0.000) while the expression of NPTX-2 in the brain tissue of AD rats was significantly increased (P = 0.000). Baicalin can play a therapeutic role by downregulating NPTX-1, upregulating NPTX-2, and downregulating CPR in AD model rats.

Changes in rat spatial learning and memory as well as serum exosome proteins after simultaneous exposure to 1.5 GHz and 4.3 GHz microwaves

This study aimed to elucidate the effects and biological targets sensitive to simultaneous 1.5 and 4.3 GHz microwave exposure in rats. A total of 120 male Wistar rats were divided randomly into four groups: the sham (S group), 1.5 GHz microwave exposure (L group), 4.3 GHz microwave exposure (C group) and simultaneous 1.5 and 4.3 GHz microwave exposure (LC group) groups. Spatial learning and memory, cortical electrical activity, and hippocampal ultrastructure were assessed by the Morris Water Maze, electroencephalography, and transmission electron microscopy, respectively. Additionally, serum exosomes were isolated by ultracentrifugation and assessed by Western blotting, nanoparticle tracking and transmission electron microscopy. The serum exosome protein content was assessed by label-free quantitative proteomics. Impaired spatial learning and memory decreased cortical excitability, and damage to the hippocampal ultrastructure were observed in groups exposed to microwaves, especially the L and LC groups. A total of 54, 145 and 296 exosomal proteins were differentially expressed between the S group and the L, C and LC groups, respectively. These differentially expressed proteins were involved in the synaptic vesicle cycle and SNARE interactions during vesicular transport. Additionally, VAMP8, Syn7 and VMAT are potential serum markers of simultaneous microwave exposure. Thus, exposure to 1.5 and 4.3 GHz microwaves induced impairments in spatial learning and memory, and simultaneous microwave exposure had the most severe effects.

Effects of dietary polyunsaturated fatty acids on corticosterone concentrations and spatial learning in rats

Dietary intake of polyunsaturated fatty acids (PUFAs) is crucial for neuronal functions, can positively affect cognition, and reduce glucocorticoid (e.g. corticosterone) concentrations in response to stress. We investigated the effects of walnut oil high in PUFAs on spatial cognition and fecal corticosterone metabolite (FCM) concentrations under non-stressed conditions in rats. Unexpectedly, PUFA-supplemented rats had higher FCM concentrations and elevated concentrations generally impaired learning in the subsequent T-maze task. Statistically adjusting for individual FCM concentrations, however, revealed that learning performance was improved in PUFA-supplemented rats. The results suggest that glucocorticoids can modulate the effects of PUFAs on spatial learning under normal (non-stressed) conditions and call for consideration of basal physiological conditions in spatial learning tasks.

Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway.

Traumatic brain injury (TBI) is a predominant cause of death and permanent disability globally. In recent years, much emphasis has been laid on treatments for TBI. Increasing evidence suggests that human umbilical cord mesenchymal stem cells (HUCMSCs) can improve neurological repair after TBI. However, the clinical use of HUCMSCs transplantation in TBI has been limited by immunological rejection, ethical issues, and the risk of tumorigenicity. Many studies have shown that HUCMSCs-derived exosomes may be an alternative approach for HUCMSCs transplantation. We hypothesized that exosomes derived from HUCMSCs could inhibit apoptosis after TBI, reduce neuroinflammation, and promote neurogenesis. A rat model of TBI was established to investigate the efficiency of neurological recovery with exosome therapy. We found that exosomes derived from HUCMSCs significantly ameliorated sensorimotor function and spatial learning in rats after TBI. Moreover, HUCMSCs-derived exosomes significantly reduced proinflammatory cytokine expression by suppressing the NF-κB signaling pathway. Furthermore, we found that HUCMSC-derived exosomes inhibited neuronal apoptosis, reduced inflammation, and promoted neuron regeneration in the injured cortex of rats after TBI. These results indicate that HUCMSCs-derived exosomes may be a promising therapeutic strategy for TBI.

Expression of Genes Regulating Synaptic Plasticity in the Hippocampus and Spatial Learning in Rats of Different Age with Streptozotocin-Induced Diabetes

Expression of Genes Regulating Synaptic Plasticity in the Hippocampus and Spatial Learning in Rats of Different Age with Streptozotocin-Induced Diabetes

Paradoxical Enhancement of Spatial Learning Induced by Right Hippocampal Lesion in Rats

The left–right hemispheric differences in some brain functions are well known in humans. Among them, savant syndrome has unique features, such as exceptional abilities in vision, memory, computation, and music, despite brain abnormalities. In cases of acquired savant and transient savant, brain damage or inhibition is often seen in the left hemisphere, suggesting a link between left hemispheric dysfunction and these talents. On the other hand, some functional left–right differences have been reported in rodent brains, and therefore, unilateral damage in rodents may also result in savant-like enhancements. In the present study, we examined the effects of hippocampal damage on spatial learning in rats with left, right, or bilateral hippocampal lesion. The results showed that learning performance was impaired in the bilateral lesion group, and there was no significant difference in the left lesion group, while performance was enhanced in the right lesion group. These results suggest that damage to the right hippocampus in rats may lead to savant-like enhancement in learning and memory. The construction of the savant model through these results will contribute to the neuroscientific elucidation of the paradoxical phenomenon observed in savants, that some abilities are enhanced despite their brain dysfunction.

MicroRNA-132-3p alleviates neuron apoptosis and impairments of learning and memory abilities in Alzheimer’s disease by downregulation of HNRNPU stabilized BACE1

ABSTRACT Alzheimer’s disease (AD) is a progressive neuro-degenerative disease characterized by dementia. MicroRNAs (miRNAs) are involved in many diseases, including AD. MiR-132-3p has been identified to be downregulated in AD. In this study, we explored the effects of miR-132-3p on neuron apoptosis and impairments of learning and memory abilities. Aβ1-42-stimulated SH-SY5Y cells were used as in vitro models of AD. An AD-like homocysteine (Hcy) rat model was established to evaluate the effects of miR-132-3p on AD pathogenesis in vivo. RIP, RNA pull down and luciferase reporter assays were conducted to investigate the relationship between miR-132-3p and its downstream target genes. The viability and apoptosis of SH-SY5Y cells were measured by CCK-8 and TUNEL assays. The rat spatial learning and memory abilities were accessed using Morris water maze test. Results indicated that miR-132-3p was downregulated in SH-SY5Y cells after Aβ1-42 treatment and promoted cell apoptosis. Mechanistically, miR-132-3p targeted heterogeneous nuclear ribonucleoprotein U (HNRNPU). HNRNPU acted as an RNA binding protein (RBP) to regulate the mRNA stability of β-site amyloid precursor protein cleaving enzyme 1 (BACE1). Overexpression of HNRNPU or BACE1 reversed the effects of miR-132-3p overexpression on the viability and apoptosis of Aβ1-42-treated SH-SY5Y cells. In vivo experiments revealed the downregulation of miR-132-3p in the hippocampus of Hcy-treated rats. MiR-132-3p suppressed levels of apoptotic genes in hippocampus and reduced impairments of learning and memory abilities in Hcy-treated rats. In conclusion, miR-132-3p reduces apoptosis of SH-SY5Y cells and alleviates impairments of learning and memory abilities in AD rats by modulating the HNRNPU/BACE1 axis.

Effect of Visual Experience on Spatial Learning of Rats

Background: Visual information acquired through observation plays a pivotal role in learning a movement pattern and motor control. Objectives: This study aimed to analyze the effect of visual deprivation on learning in rats. Methods: The study sample consisted of 12 male rats, divided into three groups. Group I consisted of four rats and was considered the control group. Transection of the two optic nerves was performed on rats of group II on the seventh day after birth and group III on the seventh week after birth to develop the early blind and late blind models, respectively. A T-shaped maze device was utilized to evaluate the learning behavior of rats. Rats of groups II and III were blinded by the optic nerve surgery. In total, 20 trials per day were conducted for nine consecutive days, in which the time and number of correct arm entries were recorded. The ANOVA and Kruskal-Wallis tests were employed to analyze the results in SPSS software (version 16.0). A p-value of less than 0.05 was considered statistically significant. Results: There was a significant difference between the three groups regarding the number of correct arm entries on days one, three, and seven (P&lt;0.05). There was also a significant difference between the three groups regarding how long it took them to enter the target box on days two and three (P&lt;0.05). Group III had a lower number of entries to the target box and it took them a significantly longer time to enter the target box, compared to the other groups. Conclusion: According to the results, visual deprivation may affect the learning of rats during the early days; however, their learning levels increased over the following days. Moreover, the early blinded rats had a higher level of learning than the lately blinded adult rats and the same level of learning as that of the sighted adult rats.

Investigation of the Possible Protective Effects of Ketamine and Dantrolene on the Hippocampal Apoptosis and Spatial Learning in Rats Exposed to Repeated Electroconvulsive Seizures as a Model of Status Epilepticus.

To evaluate the possible neuroprotective effects of ketamine and dantrolene on the hippocampal apoptosis and spatial learning in rats exposed to repeated electroconvulsive seizures (ECS) as a model of status epilepticus (SE). Twenty-four rats were assigned to 4 groups. 1st Group was Sham. 2nd Group was ECS: ECS was induced by ear electrodes via electrical stimulation. The same ECS protocol was applied to the 3th and 4th Groups which received ketamine (40 mg/kg s.c.) or dantrolene (5 mg/kg i.p.) 1 h before each ECS, respectively. Following 30 days of recovery, the cognitive status of the animals was evaluated via Morris Water Maze (MWM). The same experimental protocol was repeated 14 days afterward to evaluate the retention of the memory. Hippocampal apoptosis was examined in corresponding experimental groups. All the animals in four groups learned the task with no significant difference between groups in MWM. The ECS+ketamine group showed memory impairment 14 days afterward. ECS+dantrolene group was not different from controls. ECS caused long term apoptotic processes in dentate gyrus (DG) and non-apoptotic neuronal injury in CA1 and CA2. Dantrolene and ketamine inhibited apoptosis and showed neuroprotective effects. Although ketamine and dantrolene inhibited ECS-induced apoptosis and non-apoptotic injury, they did not produce similar effects on memory retention. It will be warranted to evaluate cognitive dysfunction by taking into consideration the other factors in addition to apoptosis and neurodegenerative changes.

Lesions to the lateral mammillary nuclei disrupt spatial learning in rats.

The head direction (HD) signal is thought to originate in the reciprocal connections between the dorsal tegmental nuclei (DTN) and the lateral mammillary nuclei (LMN) and lesions to these structures disrupt the HD signal in downstream structures. Lesions to the DTN also disrupt performance on spatial tasks where directional heading is thought to be important. In Experiment 1, rats with bilateral electrolytic lesions of the LMN and sham controls were trained on 2 tasks previously shown to be sensitive to DTN damage. Rats were first trained on either a direction or rotation problem in a water T maze. LMN-lesioned rats were impaired relative to sham controls, on both the first block of 8 trials and on the total number of trials taken to reach criterion. In the food-foraging task, rats were trained to leave a home cage at the periphery of a circular table, find food in a food cup at the center of the table, and return to the home cage. Again, LMN-lesioned rats were impaired relative to sham rats, making more errors on the return component of the foraging trip. In Experiment 2, rats with electrolytic LMN lesions were also impaired on a dry land version of the direction and rotation problems and had difficulty discriminating between reinforced and nonreinforced locations on a 12-arm maze. These results build on previous behavioral and cell-recording studies and demonstrate the importance of the direction system to spatial learning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The Effect of High-Intensity Interval Training with and Without Caloric Restriction on Spatial Learning and Long-Term Memory of Obese Rats

Background: Increasing fat mass in the body reduces long-term memory (LTM) and spatial learning (SL). Objectives: The purpose of this study was to compare the effects of high-intensity interval training (HIIT) with and without caloric restriction (CR) on SL and LTM of obese rats. Methods: Forty male Sprague Dawley rats were subjected to a high-fat diet (HFD) for 12 weeks. After confirmation of obesity, they were divided into four groups of 10 subjects, including (1) training (T), (2) training + caloric restriction (T+CR), (3) CR, and (4) obese control (OC). Also, to assess the effect of obesity on the research variables, 10 rats were considered the standard control (SC) group. For 8 weeks, the rats in groups 1 and 2 performed HIIT three times per week at an intensity of 80% to 95% of Vo2max, and groups 2 and 3 received CR of 60%. Results: LTM and SL were significantly decreased by obesity (P = 0.001); T, CR and T + CR had a significant effect on LTM (P = 0.001); T and T + CR caused a significant increase in SL (P = 0.001). However, the CR did not have a significant effect on SL (P = 0.069). Conclusions: It seems that HIIT, and somewhat the CR, by itself has contributed to the improvement of the cognitive impairment of obesity. Also, the interaction of T and CR was effective in improving these disorders, but its effect was not more intense than each one alone.

Physical activity as an option to reduce adverse effect of EMF exposure during pregnancy

The popularity of using wireless fidelity over the last decades increased apprehensions about impact of high frequency electromagnetic fields (EMF) on health. Most of previous studies mentioned adverse effect of EMF on cognitive processes, but so far, no study has provided a way to control adverse effects of EMF exposure. The purpose of this study was to examine the effect of Wi-Fi EMF and physical activity on spatial learning and motor function in pregnant rat’s offspring. Forty Albino-Wistar pregnant rats divided randomly into four groups (EMF, physical activity, combined 2.4GHZ EMF and physical activity and control groups). For assessing spatial learning in 56 post-natal days’ old (PND) male offspring, Morris Water Maze (MWM) was used and to examine motor function Open-field test was taken. Although results of MWM test revealed that Wi-Fi modem EMF caused impairment in spatial learning in rats exposed to EMF but physical activity could reduce negative effect of EMF in pregnant rat’s offspring who exposed during pregnancy but performed swimming. In addition, results of open-field test showed that litter’s motor function in EMF group significantly declined in comparison with physical activity and combined 2.4GHZ EMF and physical activity groups. According to our findings, it can be concluded that execution physical activity individually or along with wave-exposed pregnancy can significantly progressive effect on offspring' cognitive and motor functions.

0095 The Effect of Chronic Intermittent Hypoxia (CIH) on Spatial Learning in Rats

0095 The Effect of Chronic Intermittent Hypoxia (CIH) on Spatial Learning in Rats

Astragaloside Ⅳ Protects Against Aβ1-42-induced Oxidative Stress, Neuroinflammation and Cognitive Impairment in Rats.

Objective To investigate the neuroprotective action of astragaloside Ⅳ (AS-Ⅳ) on spatial learning and memory impairment induced by amyloid-beta 1-42 (Aβ1-42) in rats and elucidate its underlying molecular mechanisms. Methods Adult-male Sprague-Dawley rats (230-250 g) were divided into six groups randomly: control, Aβ1-42, AS-Ⅳ, Aβ1-42 plus 5 mg/kg·d AS-Ⅳ, Aβ1-42 plus 25 mg/kg·d AS-Ⅳ, and Aβ1-42 plus 50 mg/kg·d AS-Ⅳ groups. Aβ1-42 were delivered by intracerebroventricular injection under the guidance of a brain stereotaxic apparatus. The Morris water maze test (hidden platform test, probe trials, visible platform test) was performed one week after Aβ1-42 injection to obtain the ability of rat spatial learning and memory. AS-Ⅳ (5, 25 and 50 mg/kg·d) was administrated intraperitoneally once per day from the 8th day after Aβ1-42 injection for 5 consecutive days. Average escape latencies, distances for searching for the platform under water and the percentage of total time elapsed and distance swam in the right quadrant after removing platform were determined by behavior software system. The vision and swim speeds of rats were also determined to exclude the effect of these factors on the parameters of learning and memory. After behavioral tests, the rats were sacrificed immediately by decapitation. Hippocampus were collected. The enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and catalase (CAT) in the hippocampus obtained from different-treated rat brain were measured by following the manufacturer's instructions. The levels of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in tissue lysates were assayed with ELISA. Results The water maze test results indicated that chronic treatments with AS-Ⅳ effectively protected the rats from Aβ1-42-induced spatial learning and memory impairment. Furthermore, the activities of SOD, GSH-px and CAT decreased by Aβ1-42 were also restored by AS-Ⅳ treatment in the hippocampus of rats. In addition, AS-Ⅳ significantly decreased the levels of IL-1β and TNF-α in the hippocampus of Aβ1-42-induced amnesia's rats. Conclusion Our findings suggest that AS-Ⅳ might be a useful chemical in improving the spatial memory and relieving the oxidative stress and neuroinflammation in Alzheimer patients.

Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP). In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to generate Fmr1 knockout (KO) rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1exon4-KO). Electrophysiological analysis revealed that the theta-burst stimulation (TBS)–induced long-term potentiation (LTP) and the low-frequency stimulus (LFS)–induced long-term depression (LTD) were decreased in the hippocampal Schaffer collateral pathway of the Fmr1exon4-KO rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) was also impaired. Consistent with previous reports, the Fmr1exon4-KO rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG)–induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1exon4-KO rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1exon4-KO rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1exon4-KO rats constitute a novel rat model of FXS that complements existing mouse models.

Reproductive experience modified dendritic spines on cortical pyramidal neurons to enhance sensory perception and spatial learning in rats.

Behavioral adaptations during motherhood are aimed at increasing reproductive success. Alterations of hormones during motherhood could trigger brain morphological changes to underlie behavioral alterations. Here we investigated whether motherhood changes a rat’s sensory perception and spatial memory in conjunction with cortical neuronal structural changes. Female rats of different statuses, including virgin, pregnant, lactating, and primiparous rats were studied. Behavioral test showed that the lactating rats were most sensitive to heat, while rats with motherhood and reproduction experience outperformed virgin rats in a water maze task. By intracellular dye injection and computer-assisted 3-dimensional reconstruction, the dendritic arbors and spines of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons were revealed for closer analysis. The results showed that motherhood and reproductive experience increased dendritic spines but not arbors or the lengths of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons. In addition, lactating rats had a higher incidence of spines than pregnant or primiparous rats. The increase of dendritic spines was coupled with increased expression of the glutamatergic postsynaptic marker protein (PSD-95), especially in lactating rats. On the basis of the present results, it is concluded that motherhood enhanced rat sensory perception and spatial memory and was accompanied by increases in dendritic spines on output neurons of the somatosensory cortex and CA1 hippocampus. The effect was sustained for at least 6 weeks after the weaning of the pups.

FRI-361 - Sildenafil Reduces Neuroinflammation and Restores Spatial Learning in Rats with Hepatic Encephalopathy. Underlying Mechanisms

FRI-361 - Sildenafil Reduces Neuroinflammation and Restores Spatial Learning in Rats with Hepatic Encephalopathy. Underlying Mechanisms

High-fat diet induces learning and memory impairments and hippocampal dendritic spine density in rats

Objective To explore the influence of high fat diet on learning and memory, as well as the alteration of the number of neurons and morphology of dendritic spines in rat hippocampi. Methods 24 male adult SD rats were randomly assigned to high fat diet group or control group. The rats were fed with high-fat diet or standard laboratory rodent chow diet for 12 weeks. Learning and memory were tested by Morris water maze and object recognition tests, and mood and motor ability were tested by open field tests.Golgi staining detected dendritic spine density of hippocampal neurons, and Nissl staining was used to observe the number of hippocampal neurons and pathological changes. Results High-fat diet induced rat spatial learning deficits, which was demonstrated by the prolonged escape latency ((38.50±9.70)s, (20.08±7.35)s, (19.96±10.56)s, (22.75±12.51)s, (14.56±4.82)s) compared with the control ((33.61±12.41)s, (14.25±7.89)s, (15.06±7.59)s, (5.53±2.81)s, (4.7±1.58)s). The spatial memory deficits demonstrated that the latency reaching platform ((30.46±21.43)s) was prolonged compared with control ((5.18±1.33)s). The working memory was impaired, which was demonstrated by the prolonged escape latency compared with control group(P<0.05). Discrimination index lowered than control group ((0.67±0.12) vs (0.81±0.08)), and the difference was significant (P=0.038), but no anxiety behaviors were observed(P=0.461). The neuron number of hippocampal neurons and dendritic spine density were significantly lowered than those in the control group((209.73±24.29)vs(262.2±18.94), (17.9±2.84)vs(21.93±2.56), respectively)(P<0.05). Conclusion Intake of high-fat diet can impair learning and memory in rats, as well as decrease the number of neurons and the density of dendritic spines in the hippocampus. Key words: High fat diet; Cognitive impairment; Hippocampus; Dendritic spine