Spatial Memory In Rats Research Articles

Comparative Study of Injected Alzheimer's Disease Models in Rats: Insights from Experimental Research.

Alzheimer's disease (AD) remains incurable, highlighting the need for new and diverse animal models to better understand its complex mechanisms. This study compares various injected animal models of AD, focusing on the main theories that explain the disease; Methods: Female Wistar rats (10-months old) were administered intracebroventricularly by artificial cerebrospinal fluid (aCSF) (Control), beta amyloid Aβ1-42 (BA), okadaic acid (OKA), lipopolysaccharides (LPS), buthionine sulfoximine (BSO) or by a mixture of these different molecules (MLG). Cognitive performance was assessed one week or one month after stereotaxic surgery; Results: Our results, show that only the Aβ and the MLG induced a persistence and progressive deficits in the working memory, recognition memory and spatial memory in rats. As the hippocampus (HIP) and the prefrontal cortex (PFC) are particularly involved in memory behavior, we analyzed long-term neuroadaptations in these brain subregions using spectrophotometric and histological methods to assess oxidative stress changes and neuronal loss, respectively. We found that the behavioral impairments in memory and learning were accompanied by irreversible oxidative stress changes and neurodegenerescence, particularly in the HIP; Conclusions: This study provides promising data on the modeling of AD in order to develop an effective therapeutic approach.

Protective effect of menthol against thioacetamide-induced hepatic encephalopathy by suppressing oxidative stress and inflammation, augmenting expression of BDNF and α7-nACh receptor, and improving spatial memory

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that can occur in people with acute or chronic liver disease. Here, we investigated the effects of menthol, a natural monoterpene, on HE induced by thioacetamide (TA) in male Wistar rats. The rats received 200 mg/kg of TA twice a week for four weeks and were administered 10 mg/kg of menthol intraperitoneally daily for the same period. The results showed that menthol treatment reduced oxidative stress and inflammation in the livers and hippocampi of the rats that received TA. It also lowered the levels of ammonium and liver enzymes AST, ALT, ALP, and GGT in the serum of these animals and prevented liver histopathological damage. In addition, the expression and activity of acetylcholinesterase in the hippocampus of HE model rats were decreased by menthol. Likewise, this monoterpene reduced the expression of TLR4, MyD88, and NF-κB in the hippocampus while increasing the expression of BDNF and α7-nACh receptor. Menthol also reduced neuronal death in the hippocampal cornu ammonis-1 and dentate gyrus regions and reduced astrocyte swelling, which led to improved learning and spatial memory in rats with HE. In conclusion, the study suggests that menthol may have strong protective effects on the liver and brain, making it a potential treatment for HE and neurodegenerative diseases.

Rats show up to 72h of significant retention for spatial memory in the radial maze.

This study explored long-term retention of spatial memory in rats using an eight-arm radial maze. Crystal and Babb (Learning and motivation, 39(4), 278-284, 2008) previously demonstrated that rats could retain spatial memory for up to 25h in the radial maze. Notably, they found performance improved with 48-h intertrial intervals compared with 24-h intervals. Our study investigated the effects of extending intertrial intervals on long-term retention of spatial memory by reducing the potential for proactive interference. Each trial comprised a learning phase, during which subjects were required to sequentially visit four randomly selected arms, followed by a free-choice test that included all eight arms, conducted after increasing the retention and intertrial intervals. The retention intervals were systematically increased from 1h to 24, 48, and, ultimately, 72h, with corresponding intertrial intervals expanding from 24 to 48, 120, and 144h. Performance significantly surpassed chance levels across all conditions, demonstrating that rats are capable of retaining spatial memory for up to 72h.

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.

Enhanced Novel Object Recognition and Spatial Memory in Rats Selectively Bred for High Nicotine Preference.

This study examined the influence of genetic background on cognitive performance in a selectively bred high nicotine-preferring (NP) rat line. Using the novel object recognition (NOR), novel location recognition (NLR), and Morris water maze (MWM) tests, we evaluated object memory, spatial memory, and spatial navigation in nicotine-naive NP rats compared to controls. Our results demonstrate that in the NOR test, both male and female NP rats spent more time exploring the novel object (higher discrimination index) compared to sex-matched controls. In the NLR, the discrimination index differed significantly from zero chance (no preference) in both NP males and females but not in controls, indicating enhanced spatial memory in the NP line. During MWM acquisition, the NP groups and control males took a shorter path to reach the platform compared to control females. On the probe trial, the distance traveled in the target quadrant was longer for NP males and females compared to their respective controls, suggesting enhanced spatial navigation and learning in the NP rats. The interesting preference for novel objects and locations displayed by NP rats may indicate a potential novelty-seeking phenotype in this line. These results highlight the complex interplay between genetic factors, cognitive function, and nicotine preference.

Evaluation and Comparison of Fullerene (C60) Aqueous Suspension Administration Effects with Memantine HCL in Rat Model of Alzheimer’s Disease Considering Behavioral Patterns and Spatial Memory

: Alzheimer's disease (AD) is among the most prevalent neurodegenerative disorders leading to dementia in the elderly. The accumulation of amyloid-beta (Aβ) plaques and the formation of tau protein tangles are primary contributors to AD, which induce oxidative stress. Fullerene C60, a nanoscale carbon allotrope with a diameter of 0.7 nanometers, stands out due to its structure rich in double bonds, making these nanoparticles effective radical scavengers. This property nominates them for potential use in treating neurodegenerative diseases like AD. In this study, unmodified pristine fullerene (C60), a highly hydrophobic molecule, was dispersed in water and administered intraperitoneally (1 mL, BID) to rats after inducing an AD-like condition with scopolamine hydrobromide (2mg/kg, i.p.). The aim was to assess the impact of fullerene (C60) treatment on cognitive behavior and spatial memory in rats, compared to the standard treatment with memantine HCL, using the Morris water maze method. The fullerene aqueous suspension (FAS) was prepared using a solvent exchange method involving a toluene/water mixture and ultrasonication. The concentration of fullerene particles in water was determined by high-performance liquid chromatography (HPLC) to be 21 µg/mL. The Dynamic Light Scattering (DLS) technique measured the average size and zeta potential of the nanoparticles as 119.14 ± 3.38 nm and -12.22 ± 5.98 mV, respectively. Treatment with FAS significantly improved memory impairment in rats compared to memantine HCL (10 mg/kg, i.p.) treatment. All rats survived until the end of the study, indicating no acute toxicity from FAS administration. These results may offer new insights into combating AD by introducing fullerene C60 as a promising nanoparticle with beneficial effects on behavioral patterns.

Effect of thymol on oxidative stress and reelin signaling pathway in Alzheimer's disease model.

The purpose of this study was to investigate how thymol affects cognitive functions and the levels of MDA, GSH, Aβ1-42, ApoE, reelin, and LRP8 in an AD model induced in male Wistar albino rats with the application of D-galactose (D-gal) and aluminum chloride (AlCl3). In this work, 3-month-old male Wistar albino rats were used. Group 1 served as the Control, Group 2 received 0.5 mL/day saline + 0.5 mL/day sunflower oil, Group 3 was administered 200 mg/kg/day AlCl3 + 60 mg/kg/day D-gal, Group 4 received 30 mg/kg/day thymol, and Group 5 was administered 200 mg/kg/day AlCl3 + 60 mg/kg/day D-gal + 30 mg/kg/day thymol. At the end of the 10-week experimental period, behavioral and memory tests were performed. GSH and MDA levels were measured in the obtained serum and brain tissue samples, while Aβ1-42, ApoE, reelin, and LRP8 levels were measured in brain tissue samples. Statistical analyses were performed using ANOVA test in Graphpad Prism V8.3 program. A p-value <0.05 was considered significant in intergroup analyses. When the novel object recognition test (NORT) results were evaluated, the Alzheimer + thymol (ALZ+TYM) group showed a significant increase in the recognition index (RI) and discrimination index (DI) compared to the Alzheimer (ALZ) group at the 24th hour. Thymol reduced working memory errors (WME), reference memory errors (RME), and maze completion time at 48, 72, and 96 hours when evaluated in terms of spatial memory in rats with Alzheimer's disease. Furthermore, Aβ1-42 and ApoE levels were increased in the ALZ group compared to the control (C), while reelin and LRP8 levels were decreased in the ALZ group compared to the C group. The data we obtained suggest that thymol may play an effective role in cognitive processes against AD and have an anti-Alzheimer's disease effect.

Metabolic dysfunction induced by HFD + L-NAME preferentially affects hippocampal mitochondria, impacting spatial memory in rats.

High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O2) consumption related to ATP production, with no changes in H2O2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD + L-NAME rats, with no alterations in other morphology-related proteins. Consistently, HFD + L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H2O2 production. Calcium uptake rate and retention capacity in the neocortex of HFD + L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning, whereas neocortical function remains unaffected.

Glucose Fluctuation Inhibits Nrf2 Signaling Pathway in Hippocampal Tissues and Exacerbates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats.

This research investigated whether glucose fluctuation (GF) can exacerbate cognitive impairment in streptozotocin-induced diabetic rats and explored the related mechanism. After 4 weeks of feeding with diets containing high fats plus sugar, the rat model of diabetes mellitus (DM) was established by intraperitoneal injection of streptozotocin (STZ). Then, GF was triggered by means of alternating satiety and starvation for 24 h. The weight, blood glucose level, and water intake of the rats were recorded. The Morris water maze (MWM) test was carried out to appraise the cognitive function at the end of week 12. Moreover, the morphological structure of hippocampal neurons was viewed through HE and Nissl staining, and transmission electron microscopy (TEM) was performed for ultrastructure observation. The protein expression levels of Nrf2, HO-1, NQO-1, Bax, Bcl-2, and Caspase-3 in the hippocampal tissues of rats were measured via Western blotting, and the mRNA expressions of Nrf2, HO-1, and NQO-1 were examined using qRT-PCR. Finally, Western blotting and immunohistochemistry were conducted to detect BDNF levels. It was manifested that GF not only aggravated the impairment of spatial memory in rats with STZ-induced type 2 DM but also stimulated the loss, shrinkage, and apoptosis of hippocampal neurons. Regarding the expressions in murine hippocampal tissues, GF depressed Nrf2, HO-1, NQO-1, Bcl-2, and BDNF but boosted Caspase-3 and Bax. GF aggravates cognitive impairment by inhibiting the Nrf2 signaling pathway and inducing oxidative stress and apoptosis in the hippocampal tissues.

Toxicity of products of thermal oxidative degradation of nitrogen-containing building polymer materials

Introduction. In the event of fires in residential premises in which nitrogen-containing thermal insulation materials (foam rubber, polyisocyanurate foam) are used, the victims will be exposed to toxic thermal degradation products. Data on long-term disorders caused by intoxication by thermal degradation products of these materials could not be found in the available literature. The aim of the study was to assess the toxicity of the products of thermal oxidative degradation of nitrogen-containing thermal insulation materials, both in the early and long-term post-intoxication period. &#x0D; Material and methods. Static inhalation intoxication of rats with products of thermooxidative destruction of polyfoam and polyisocyanurate foam (at a concentration of 0,8HLC50) was simulated. The concentration of carboxyhemoglobin in the blood of rats, indicators of vital functions were determined immediately before and on days 1, 7 and 28 after exposure. To assess learning disabilities in rats, a conditioned reflex of active avoidance by swimming was developed. To assess spatial memory in rats, the method of developing and reproducing the conditioned reflex of searching for food was used.&#x0D; Results and discussion. The intoxication of rats with products of thermooxidative destruction of the studied materials of moderate severity was simulated. Violations of the functions of the respiratory and cardiovascular system of rats in the early (7 days) and long-term (28 days) post-intoxication period were not detected. In the long-term (28 days) post-intoxication period, an increase in the duration of the latent period of active avoidance by swimming of rats was determined (compared with the control), an increase in the number of spatial memory errors in rats and the time of testing (compared with the control) was revealed.&#x0D; Limitation of the study. Limitations are due to the methodology of the research being conducted. A quantitative analysis of only some gaseous products of thermal oxidative destruction was perfomed.&#x0D; Conclusion. It was found that intoxication of rats with products of thermooxidative destruction of foam rubber and foam polyiysocyanurate (at a concentration of 0,8HLC50) led to impaired learning and spatial memory of rats in the long-term post-intoxication period.

The impact of early life stress and schizophrenia on motor and cognitive functioning: an experimental study

BackgroundEarly life stress (ELS) and parental psychopathology, such as schizophrenia (SZ), have been associated with altered neurobiological and behavioral outcomes later in life. Previous studies have investigated the effects of ELS and parental SZ on various aspects of behavior, however, we have studied the combined effects of these stressors and how they interact, as individuals in real-life situations may experience multiple stressors simultaneously.ObjectiveThe aim of this study was to investigate the impact of ELS and schizophrenia on locomotor activity, anxiety-like behavior, exploratory tendencies, and spatial memory in Sprague Dawley (SD) rats.MethodsMale and female SD pups were randomly assigned to eight groups: control, ELS, schizophrenia, and ELS + schizophrenia. ELS was induced by prenatal stress (maternal stress) and maternal separation (MS) during the first 2 weeks of life, while SZ was induced by subcutaneous administration of ketamine. Behavioral tests included an open field test (OFT) for motor abilities and a Morris water maze (MWM) for cognitive abilities. ANOVA and post hoc Tukey tests were utilized to analyze the data.ResultsOur results show that ELS and parental psychopathology had enduring effects on SZ symptoms, particularly psychomotor retardation (p &amp;lt; 0.05). The OFT revealed increased anxiety-like behavior in the ELS group (p = 0.023) and the parental psychopathology group (p = 0.017) compared to controls. The combined ELS and parental psychopathology group exhibited the highest anxiety-like behavior (p = 0.006). The MWM analysis indicated impaired spatial memory in the ELS group (p = 0.012) and the combined ELS and parental psychopathology group (p = 0.003) compared to controls. Significantly, the exposure to ELS resulted in a decrease in the population of glial fibrillary acidic protein-positive (GFAP+) astrocytes. However, this effect was reversed by positive parental mental health.ConclusionOur findings highlight the interactive effects of ELS and parental psychopathology on anxiety-like behavior and spatial memory in rats. ELS was linked to increased anxiety-like behavior, while SZ was associated with anhedonia-like behavior. Positive parenting augments neuroplasticity, synaptic function, and overall cognitive capacities.

Consequences of adolescent social isolation on behavior and synaptic plasticity in the dorsal and ventral hippocampus in male Wistar rats

ABSTRACT Objective Social interaction at a young age plays a critical role in the normal maturation of the brain and neuroendocrine system. Deprivation of social contacts has been associated with numerous cognitive and emotional abnormalities. However, neurobiological mechanisms that may underlie these effects remain poorly understood. In the present study, we examined the effect of 4–6-week social isolation during the adolescent period on rat spatial memory and emotional responses and investigated synaptic plasticity in the dorsal (DH) and ventral hippocampus (VH), which are known to be differently involved in these behaviors. Methods Male Wistar rats were housed individually or in groups of four for 4–6 weeks immediately after weaning. At the end of the isolation period, rats were subjected to behavioral testing or electrophysiological studies. Behavioral tests included behavioral excitability, sucrose preference, open field (OF), elevated plus maze (EPM), Morris water maze (MWM), and Y-maze test. For plasticity experiments, long-term potentiation (LTP) in Schaffer collateral/СA1 synapses was induced using high-frequency stimulation (HFS) on transverse hippocampal slices. Results Social isolation induced hyperexcitability, increased anxiety- and anhedonia-like behaviors, while no significant changes were observed in cognitive tasks. Electrophysiological recordings revealed enhanced short-term potentiation (STP) in the VH and suppressed LTP in the DH of isolated animals compared to group-housed controls. Conclusions Our findings suggest that adolescent social isolation has distinct effects on synaptic plasticity in the VH and DH and leads to emotional dysregulation rather than impairments in cognitive performance.

Refinement of the Barnes and Morris water maze protocols improves characterization of spatial cognitive deficits in the lithium-pilocarpine rat model of epilepsy

Temporal lobe epilepsy (TLE) often causes cognitive impairment, especially a decline in spatial memory. Reductions in spatial memory and learning are also common in rodent models of TLE. The Morris water maze and the Barnes maze are the standard methods for evaluating spatial learning and memory in rodents. However, animals with TLE may exhibit agitation, distress, and fail to follow the paradigmatic context of these tests, making the interpretation of experimental data difficult. This study optimized the procedure of the Morris water maze and the Barnes maze to evaluate spatial learning and memory in rats with the lithium-pilocarpine TLE model (LPM rats). It was demonstrated that LPM rats required a mandatory and prolonged habituation stage for both tests. Therefore, the experimental rats performed relatively well on these tests. Nevertheless, LPM rats exhibited a slower learning process compared to the control rats. LPM rats also showed a reduction in spatial memory formation. This was more pronounced in the Barnes maze. Also, LPM rats utilized a sequential strategy for searching in the Barnes maze and were incapable of developing a more efficient spatial search strategy that is common in control animals. The Barnes maze may be a better choice for assessing search strategies, learning deficits, and spatial memory in rats with TLE when choosing between the two tests. This is because of the risk of unexpected seizure occurrence during the Morris water maze tests, and the potential risks for animal welfare.

Endurance Exercise Training Attenuates the Waterpipe Smoke Inhaling-Induced Learning and Memory Impairment in Rats: Role of Neurotrophic Factors and Apoptotic System.

The increasing prevalence of waterpipe tobacco smoking (WTS) and its detrimental effects on memory function have been reported. This study was conducted to investigate the effect of moderate-intensity endurance exercise on the detrimental effects of WTS on learning and spatial memory in rats. Animals were divided into the Control group (CTL), the exercise group (Ex) which trained for 8 weeks, the WTS group (Wp) exposed to smoke inhalation (30 minutes per day, 5 days each week, and for 8 weeks), and the group that did exercise training and received waterpipe smoke together (Ex + Wp). Thereafter, learning and spatial memory were assessed by the Morris water maze test and hippocampal molecular measurements were done. Waterpipe smoke significantly impaired learning and spatial memory, decreased expression of neurotrophic factors IGF-1 and BDNF (p < .01 and p < .05 vs. CTL group, respectively), increased BAX to BCL-2 ratio (p < .001 vs. CTL group) in hippocampal tissue, and increased the percent of damaged neurons in the hippocampal CA1 area (p < .05 vs. CTL group). Combination of exercise training with WTS prevented learning and spatial memory disturbances and recovered expression of neurotrophic factors IGF-1 (p < .05 vs. Wp group), decreased BAX to BCL-2 ratio (p < .001 vs. Wp group), and reduced percentage of damaged neurons (p < .05 vs. Wp group). Findings suggest that moderate-intensity endurance exercise training can ameliorate learning and memory impairment caused by waterpipe smoke in rats. This effect partly results from increasing the expression of neurotrophic factors BDNF and IGF-1 and correcting pro/anti-apoptotic proteins balance in the hippocampal tissue. The popularity of WTS especially among youth is increasing. We assessed the effect of hookah smoke with/without exercise on learning and memory. Hookah smoke leads to CA1-neural injury and impairs learning and memory in rats. A combination of exercise training with hookah smoke attenuates these complications. This positive effect of exercise is partially mediated by the balancing of brain-derived neurotrophic factor (BDNF) and Insulin-like growth factor-1 (IGF-1) and also the BAX to BCL-2 ratio, a significant predictor of cell susceptibility to apoptosis. Extrapolation of these positive findings to humans needs complementary studies.

Rat spatial memory and foraging on dual radial mazes.

Three experiments are reported that used a new test of spatial memory in rats. The apparatus used was dual eight-arm radial mazes that were connected at one arm of each maze, with a start arm and doors to each maze. Rats could be forced to go to one maze or the other or could make a free choice between mazes. In Experiment 1, rats formed reference memory for the arm containing food on one maze but had food randomly placed on different arms over trials on the other maze. In Experiment 2, rats formed working memory for the arm containing food on one maze but not the other. In Experiment 3, food location changed randomly among trials on both mazes, but one maze contained a cue for the location of food. Rats used reference and working memory to go directly to the food arm on one maze but found food only after searching several arms on the other maze. Most importantly, when given free-choice trials rats developed a significant preference for the maze where they knew the location of food reward or found the cue indicating the location of reward. We suggest these findings may be best interpreted by rats applying two successive rules: (1) choose the maze that leads to the most immediate reward, and (2) use extramaze or intramaze cues to find reward location on the maze.

Moderate-intensity intermittent exercise prevents memory deficit, hippocampal neuron loss, and elevated level of Alzheimer’s dementia markers in the hippocampus of trimethyltin-induced rats

BackgroundModerate-intensity intermittent exercise (MIIE) has been proposed as an effective method for preventing Alzheimer's dementia (AD). AimThis study aimed to investigate the effects of MIIE on the spatial memory and protein level of AD markers in the hippocampus of trimethyltin (TMT)-induced rat model of hippocampal degeneration. MethodsMale Sprague Dawley (SD) rats were randomly assigned into four groups: normal control (N), exercise control (E), TMT control (T), and exercise and TMT (ET). Rats of the exercise groups (E and ET) were forced to run on a treadmill for 30 min each day at maximum for 12 weeks. Intraperitoneal injection of 8 mg/kgBW TMT was administered as a single dose, 10 days before the last exercise treatment for the T and ET groups. The spatial memory of rats was examined using Morris water maze (MWM) test after the exercise period. After euthanasia, the hippocampal tissue was dissected out and the level of hippocampal presenilin-1 (PSEN-1) and phosphorylated tau (p-tau) protein were measured using ELISA. The total number of hippocampal pyramidal neurons was estimated using unbiased stereological analysis. Qualitative immunohistochemistry was performed to examine the expression of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) in paraffin sections of the hippocampus. ResultsTMT exposure induced memory impairment indicated by the T group having the lowest percentage of time and percentage of path length in the target quadrant compared to other groups. MIIE prevented the memory impairment effect of TMT exposure indicated by the ET group having no significantly different MWM performance compared to the E and N groups. The ET group had significantly lower levels of hippocampal AD markers, p-tau and PSEN-1, as well as significantly higher estimated total number of pyramidal neurons of hippocampal CA1 and CA2–3 regions compared to the T group. Expressions of TNF-α was weak, while the expression of IL-10 was stronger in the ET group compared to the control group. The TMT-induced group exhibited stronger expression of BDNF. ConclusionMIIE prevents neuronal loss and impaired spatial memory upon TMT exposure most probably via preventing elevated levels of hippocampal AD markers and neuroinflammation. WC:350.

Alpha-Pinene Effect on the Improvement of Working and Spatial memory in Rats

Alpha-Pinene Effect on the Improvement of Working and Spatial memory in Rats

Paternal Aggression in Early-life Impairs the Spatial Memory and Passive Avoidance Learning in Adulthood of Male Rats: The Possible Role of DRD2

Introduction: Negative early-life experiences (e.g. having an aggressive father) can leave long-lastingimpacts on the behavior. However, it is not clear if they influence learning and memory. Methods: In this study, we investigated the influences that the presence of an aggressive father had on the level of passive avoidance learning and spatial memory. We also studied the changes in the dopamine receptor D2 (DRD2) and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) gene expression in the hippocampus. Then, we evaluated if a DRD2 antagonist (sulpiride, 0.125, 0.25, or 0.5 μg/rat) could modulate these changes. Results: We found that the subjects exposed to early-life stress made by aggressive fathers had impaired passive avoidance learning and spatial memory compared to subjects with normal fathers. Treatment with sulpiride improved passive avoidance learning and spatial memory in rats with aggressive fathers. The rats with aggressive fathers also had higher expression of the DRD2 gene in their hippocampus than those with normal fathers, while the PGC-1α gene expression was not different among groups. Treatment with sulpiride (0.125, 0.25, or 0.5 μg/rat) reduced the DRD2 gene expression in those with aggressive fathers to the normal level compared to those with normal fathers. Conclusion: These data suggest that having and living in a shared place with an aggressive father, even without any physical contact, can detrimentally affect passive avoidance learning and spatial memory which is accompanied by the increased expression of the DRD2 gene. Also, sulpiride as a dopaminergic antagonist could reverse this process.

The effect of crocin on cholestasis-induced spatial memory impairment with respect to the expression level of TFAM and PGC-1α and activity of catalase and superoxide dismutase in the hippocampus.

Large evidence has shown that cholestasis has a wide-range of deleterious effects on brain function, and also, on neurocognitive functions including learning and memory. On the other hand, crocin (derived from Crocus sativus) is a medicinal natural compound that induces neuroprotective and precognitive effects. In this study, we aimed to evaluate the effect of crocin on spatial learning and memory in cholestatic rats with respect to the level of mitochondrial transcriptional factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), catalase (CAT), and superoxide dismutase (SOD) in the hippocampus of male Wistar rats. Bile duct ligation (BDL) was used to induce cholestasis. Y-maze apparatus was used to assess spatial memory performance and real-time PCR was used to assess TFAM and PGC-1α gene expression. Also, crocin was injected intraperitoneal at the doses of 15, 20, and 30mg/kg for thirty days. The results showed that BDL impaired spatial memory in rats. BDL also decreased SOD, TFAM, and PGC-1α level. In addition, crocin partially reversed the impairment effect of BDL on spatial memory. Crocin (30mg/kg) also reversed the effect of BDL on SOD, TFAM, and PGC-1α. Of note, the effect of BDL on CAT activity was controversial. It seems that BDL can increase CAT activity. In addition, crocin (30mg/kg) reversed the enhancement of CAT following BDL to its control level. In conclusion, crocin may induce a significant neuroprotective effect on cholestasis-induced memory impairment.

Mesenchymal Stem Cells Therapy Led to the Improvement of Spatial Memory in Rats with Alzheimer's disease Through Changing the Expression of LncRNA TUSC7/ miR-449a/ PPARγ and CD36 Genes in the Brain Tissue.

Mesenchymal stem cells (MSCs) have the ability to phagocytize amyloid beta (Aβ) plaques and lower inflammation through the activity of microglia. Peroxisome proliferator-activated receptor gamma (PPARγ) is a protein involved in reducing inflammation through the activity of microglia and the phagocytosis of Aβ plaques by scavenger receptor CD36, in this study, the effect of MSCs therapy on memory function and plaques was investigated. A total of 24 adult male Wistar rats were randomly divided into three groups:1) the control group, 2) the Aβ-treated group (Alzheimer's disease (AD)), and 3) the MSC-treated group (AD + MSC). After the treatment with Aβ and MSCs, western blotting and real-time polymerase chain reaction (PCR) techniques were used to assess protein and gene expression levels, respectively. MSCs improved spatial learning and memory in the AD group (p ≤0.05). The expression levels of PPARγ, lncRNA TUSC7, and CD36 genes were significantly elevated in the group receiving MSCs compared to the AD group (p≤0.0001). Also, the expression level of miR-449a significantly decreased in the AD + MSC group (p≤0.0001). Moreover, western blot analysis revealed that PPARγ and CD36 protein levels were enhanced in the AD + MSC group compared to the AD group (p≤0.0001). MSC treatment led to the positive regulation of the PPARγ gene and its protein expression by ncRNAs, which could have a beneficial impact on CD36 protein levels, and subsequently, reduce the number of plaques in the cell recipient.