Memory Morris Water Maze Research Articles

Dityrosine administration induces novel object recognition deficits in young adulthood mice

Dietary modifications have been shown to contribute to the physical and mental diseases. Oxidative modifications of protein can be easily found in protein-rich food such as meat and milk products. Previous studies mainly focus on the consequences of lipid oxidation products intake in vivo, but the effects of protein oxidation products consumption have been largely neglected. Oxidants have been shown to play an important role in aging and neurodegenerative diseases. Dityrosine is the oxidated product of tyrosine residues in protein which is considered as a biomarker for oxidative stress, but the potential deleterious effects of dityrosine are unknown. In the present study, we explored the effects of dityrosine administration on the behavioral aspect. We found that dityrosine-ingested mice displayed impaired memory during novel object recognition test, but no influence to the spatial memory in Morris water maze compared with the saline group. Other aspects of neurobehavioral function such as locomotor activity, anxiety and social behavior were not affected by dityrosine ingestion. Furthermore, we found that dityrosine-ingested mice showed decreased expression level of NMDA receptor subunits Nr1, Nr2a, Nr2b as well as Bdnf, Trkb. Our study suggests that dityrosine exposure impairs hippocampus-dependent nonspatial memory accompanied by modulation of NMDA receptor subunits and Bdnf expression.

Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD.

Effect of Postnatal Chronic Lead Exposure on Spatial Learning and Memory in Male Rat

Objectives: The aim of present study was to evaluate the effects of neonatal lead exposure on spatial learning and memory in Morris water maze. Materials and Methods: In this experimental study, 30 new born male rats were randomly divided into two groups: Control and lead exposure groups. Rat pups in lead exposure group received 8 mg/kg lead acetate intraperitoneally daily for 21 days. Then, rats trained with 6 trials per day for 6 consecutive days in the water maze at 36th postnatal day (PD). Twenty four hours after ending of training, a probe test was done to measure memory retention. Results: Results of this study demonstrated that exposure to lead could affect learning as indicating by significant differences in escape latency and traveled distance between 2 groups during 6 days of training. Lead exposure group exhibited significantly higher escape latency and distance traveled during training trials compared to control group. Also, lead exposure rats had higher platform location latency than control group during probe trial (P < 0.05). Conclusions: These data suggests that lead exposure during early postnatal period of brain development causes impairment in spatial learning and memory.

Novel gamma-aminobutyric acid reuptake inhibitor improves spatial learning and memory in Morris water maze and radial arm water maze tests

Novel gamma-aminobutyric acid reuptake inhibitor improves spatial learning and memory in Morris water maze and radial arm water maze tests

Rescue of pathology and cognitive impairment by tau immunotherapy at a moderate to severe stage of the disease in 3xTg-alzheimer's disease mice

Neurofibrillary tangles which are made up of abnormally hyperphosphorylated tau are a hallmark brain lesion of Alzheimer disease (AD) and other tauopathies. Unlike normal tau which interacts with tubulin and promotes its assembly into microtubules, the AD P-tau sequesters normal tau, disrupts microtubules, and serves as a template for its prion-like aggregation and spread. In a previous study we showed that targeting the amino terminal region of tau could rescue not only tau pathology and cognitive impairment but also could possibly reduce Aβ pathology in 3xTg-AD mice. Female 12-13 month old 3xTg-AD mice and age- and sex-matched control WT mice received 6 weekly intravenous injections of 15 micrograms of mouse monoclonal antibody (mAb) 43D to Tau6-18, mAb 77E9 to Tau184-195, a mixture of 43D and 77E9 or, as control, mouse IgG for 6 weeks. The day after the last injection the animals were subjected to several days of behavioral tests. On day 66 the animals received the 7thinjection of the antibody or control IgG. One half of the mice were sacrificed on day 72 and the remaining animals were tested for reference memory and by novel object location test at age ∼18 months. 3xTg-AD mice exhibited reference memory impairment and short-term memory deficit and higher level of anxiety than WT control mice. Passive immunization with 43D antibody completely rescued deficits in reference memory in Morris Water Maze and short-term memory in one-trial object recognition task. Passive immunization with antibody 77E9 rescued short-term memory impairment but did not show beneficial effect in spatial learning. At 18 months the 3xTg-AD mice treated with antibody 43D but not 77E9 showed a clear trend in rescue of short-term reference memory deficit. These studies show (1) that targeting of the amino terminal region, i.e. tau6-18, is more beneficial than tau184-195 region; (2) that the beneficial effect of passive immunotherapy can last at least ∼5 months in mice; and (3) that targeting the amino terminal region of tau is potentially an especially promising strategy for the treatment of AD and possibly other tauopathies.

Protective effects of forced exercise against methylphenidate-induced anxiety, depression and cognition impairment in rat.

Background:Methylphenidate (MPH), a neural stimulant, can cause damages to brain; the chronic neurochemical and behavioral effects of MPH remain unclear. Exercise lowers stress and anxiety and can act as non-pharmacologic neuroprotective agent. In this study protective effects of exercise in MPH-induced anxiety, depression and cognition impairment were investigated.Materials and Methods:Seventy adult male rats were divided randomly into five groups. Group 1 served as negative control, received normal saline (0.2 ml/rat) for 21 days, group 2 and 3 (as positive controls) received MPH (10 and 20 mg/kg) for 21 days. Groups 4 and 5 concurrently were treated with MPH (10 and 20 mg/kg) and forced exercise for 21 days. On day 21, Elevated Plus Maze (EPM), Open Field Test (OFT), Forced Swim Test (FST) and Tail Suspension Test (TST) were used to investigate the level of anxiety and depression in animals. In addition between 17th and 21th days, Morris Water Maze (MWM) was applied to evaluate the effect of MPH on spatial learning and memory.Results:MPH-treated animals indicated a reflective depression and anxiety in a dose-dependent manner in FST, EPM and TST which were significantly different from the control group and also can significantly attenuate the motor activity and anxiety in OFT. Forced exercise by treadmill can attenuate MPH-induced anxiety, depression and motor activity alteration in OFT. MPH also can disturb learning and memory in MWM and forced exercise can neutralize this effect of MPH.Conclusion:We conclude that forced exercise can be protective in brain against MPH-induced anxiety, depression and cognition alteration.

Reduction of Methylphenidate Induced Anxiety, Depression and Cognition Impairment by Various doses of Venlafaxine in Rat.

Background:Methylphenidate (MPH) is a neural stimulant agent, which its neurochemical and behavioral effect remain unclear. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor antidepressant, which was used for management of depression and anxiety. In this study, protective effects of venlafaxine on MPH induced anxiety, depression and cognition impairment were investigated.Methods:Forty-eight adult male rats were divided randomly to 5 groups. Group 1, received normal saline (0.2 ml/rat) for 21 days and served as control group. Group 2, received MPH (10 mg/kg) for 21 days. Groups, 3, 4, 5 and 6 concurrently were treated by MPH (10 mg/kg) and venlafaxine at doses of 25, 50, 75 and 100 mg/kg respectively for 21 days. On day 22, elevated plus maze (EPM), open field test (OFT), forced swim test (FST) and tail suspension test (TST) were used to investigate the level of anxiety and depression in animals. In addition, between days 17 and 21, Morris water maze (MWM) was used to evaluate the effect of MPH on spatial learning and memory.Results:MPH caused depression and anxiety in a dose-dependent manner in FST, OFT, EPM and TST, which were significantly different compared with control group. Furthermore, MPH can significantly attenuate the motor activity in OFT. Venlafaxine in all doses can attenuate MPH induced anxiety, depression and motor activity alterations. MPH also can disturb learning and memory in MWM, but venlafaxine did not alter this effect of MPH.Conclusions:We conclude that venlafaxine can be protective in the brain against MPH induced anxiety and depression.

Neuronal analysis and behaviour in prenatally gamma-irradiated rats.

The intrauterinal development in mammals represents a very sensitive period of life in relation to many environmental factors, including ionizing radiation (IR). The developing nervous system is particularly vulnerable to IR, and the consequences of exposure are of importance because of its potential health risks. The aim of our work was to assess whether prenatal irradiation of rats on the 17th day of embryonic development with a dose of 1 Gy would affect the formation of new cells and the number of mature neurons in the hippocampus and the selected forms of behaviour in the postnatal period. Male progeny of irradiated and control females was tested at ages of 3 weeks, 2 and 3 months. The number of mitotically active cells in the gyrus dentatus (GD) of the hippocampus was significantly reduced in irradiated rats aged 3 weeks. In irradiated rats aged 2 months, a significant reduction of mature neurons in CA1 area and in GD of the hippocampus was observed. The IR negatively influenced the spatial memory in Morris water maze, significantly decreased the exploratory behaviour and increased the anxiety-like behaviour in elevated plus-maze in rats aged 2 months. No significant differences were observed in animals aged 3 months compared with controls of the same age. A significant correlation between the number of mature neurons in the hilus and of the cognitive performances was found. Our results show that a low dose of radiation applied during the sensitive phase of brain development can influence the level of neurogenesis in the subgranular zone of GD and cause an impairment of the postnatal development of mental functions.

Preliminary evidence that abscisic acid improves spatial memory in rats

Abscisic acid (ABA) is a crucial phytohormone that exists in a wide range of animals, including humans, and has multiple bioactivities. As direct derivatives of carotenoids, ABA and retinoic acid (RA) share similar molecular structures, and RA has been reported to improve spatial memory in rodents. To explore the potential effects of ABA on spatial learning and memory in rodents, 20mg/kg ABA was administered to young rats for 6weeks, and its effects on behaviour performance were evaluated through a series of behavioural tests. ABA pharmacokinetic analysis revealed that the exogenous ABA was distributed widely in the rat brain, characterised by rapid absorption and slow elimination. The behavioural tests showed that ABA increased both the duration spent in the target quadrant and the frequency it was entered in the probe test of the Morris water maze (MWM) and decreased the latency to locate the target quadrant. Moreover, ABA decreased the latency to enter the novel arm in the Y-maze test, accompanied by increases in the total entries and distance travelled in the three arms. However, there were no significant differences between the ABA-treated and control rats in the open field test and elevated plus-maze test. These results preliminarily indicate that ABA improves spatial memory in MWM and exploratory activity in Y-maze in young rats.

Nootropic and anti-stress effects of rice bran oil in male rats.

Rice bran oil (RBO) is an important product of rice bran. It is considered to be one of the most important nutritious oil due to its favorable fatty acid composition and unique composition of naturally occurring biologically active antioxidant compounds. This study was designed to monitor the effects of oral intake of RBO on stress response in rats. RBO was extracted using hexane. Rats were divided into Control and test (RBO-treated). RBO-treated rats were given 0.2ml/day RBO for 6weeks. Food intake and body weight changes were monitored weekly. After 6weeks open field activity and Morris Water Maze (MWM) test were performed. Results showed that weekly cumulative food intake but not body weight were lower in RBO-treated rats during 1st to 5th week of treatment, which were normalized at the end of treatment. Exploratory activity of RBO-treated rats in an open field was increased. Spatial memory in Morris water maze was enhanced in RBO-treated than control rats. An episode of 2h restraint stress decreased the 24h food intake of both control and RBO-treated animals. Behavioral deficits were lower in RBO-treated rats. Exposure of 2h restraint stress increased brain serotonin (5-hydroxytryptamine: 5-HT) metabolism. These increases were lower in RBO-treated restrained than their respective control animals. Serotonergic neurotransmitter mechanism is implicated in stress. The findings of the study show beneficial effects of RBO in learning and memory functions. Moreover, the study also highlights the attenuating effect of RBO on stress induced behavioral and neurochemical effects in rats.

Effects of rolipram and zaprinast on learning and memory in the Morris water maze and radial arm maze tests in naive mice.

Inhibition of phosphodiesterase 5 (PDE) improved recognition memory and counteracted spatial learning impairment induced by nitric oxide synthase (NOS) inhibition in recent studies. Aim of this study was to investigate effects of rolipram, a PDE4 inhibitor and zaprinast, a PDE5 inhibitor, on learning and memory in Morris water maze (MWM) and radial arm maze (RAM) tests in naive mice. Male Balb-c mice were treated subchronically with zaprinast (3 and 10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) for 6 days in the MWM test and acutely before the retention trial of radial arm maze test. Rolipram (0.05 and 0.1 mg/kg) significantly decreased escape latency between 2(nd) and 5(th) sessions, while zaprinast (10 mg/kg) significantly decreased escape latency only in 2(nd) session. Rolipram (0.05 and 0.1 mg/kg) and zaprinast (10 mg/kg) significantly increased time spent in escape platform's quadrant in probe trial of MWM test; only rolipram decreased mean distance to platform, while zaprinast had no effect on mean distance to platform. Zaprinast (3 and 10 mg/kg) significantly decreased number of errors compared to control group, while rolipram (0.05 and 0.1mg/kg) had no effect on number of errors in retention trial of RAM test. Rolipram (0.05 and 0.1 mg/kg) and zaprinast (10 mg/kg) significantly decreased time spent to complete retention trial (latency) compared to control group. Our study revealed that both zaprinast and rolipram enhanced spatial memory in MWM, while zaprinast seems to have more memory enhancing effects compared to rolipram in radial arm maze test.

Neuroprotective effect of N-acetyl cysteine against streptozotocin-induced memory dysfunction and oxidative damage in rats.

Growing evidences indicate that endogenous oxidants and antioxidant defense interact in a vicious cycle, which plays a critical role in the pathogenesis of cognitive dysfunction. In this study, we examined the effect of N-acetyl cysteine (NAC) against the intracerebroventricular infusion of streptozotocin (ICV STZ)-induced cognitive impairment and mitochondrial oxidative damage in rats. Male adult Wistar rats were injected with STZ (3 mg/kg) bilaterally through ICV. NAC (50 and 100 mg/kg) was administered for 3 weeks post-surgery. The rats were sacrificed on the 21st day following the last behavioral test, and cytoplasmic fractions of the hippocampus and cortex were prepared for the quantification of acetylcholinesterase, oxidative stress parameter, mitochondrial enzymes, inflammatory mediators and caspase-3 activity. ICV STZ resulted in poor retention of memory in Morris water maze. It also increased the mito-oxidative damage and tumor necrosis factor-α, interleukin 6 and caspase-3 levels in the hippocampus and cortex compared to sham animals. NAC significantly improved memory retention and attenuated oxidative damage parameters, inflammatory markers in STZ-treated rats. The results of the present study strongly indicate the effectiveness of NAC in preventing cognitive impairment as well as mito-oxidative stress and may be considered as a potential agent in the management of cognitive-related disorders.

Post-acquisition hippocampal NMDA receptor blockade sustains retention of spatial reference memory in Morris water maze

Several studies have demonstrated that the hippocampal N-methyl-d-aspartate type glutamate receptors (NMDARs) are necessary for the acquisition but not the retention of spatial reference memory. In contrast, a few studies have shown that post-acquisition repetitive intraperitoneal injections of an NMDAR antagonist facilitate the retention of spatial reference memory in a radial maze task. In the present study, we investigated the role of hippocampal NMDARs in the retention of spatial reference memories in Morris water maze. In Experiment 1, 24h after training (4 trials/day for 4 days), d-AP5 was chronically infused into the hippocampus of rats for 5 days. In the subsequent probe test (seven days after training), we found that rats infused with d-AP5 spent a significantly longer time in the target quadrant compared to chance level, whereas rats in the control group did not. In Experiment 2, d-AP5 was infused into the hippocampus 1 (immediate) or 7 (delayed) days after the training session. In the probe test, following the retention interval of 13 days, immediate infusion facilitated the performance in a manner similar to Experiment 1, whereas the delayed infusion did not. These findings suggest that hippocampal NMDARs play an important role in the deterioration of spatial reference memory.

Glia Protein Aquaporin‐4 Regulates Aversive Motivation of Spatial Memory in Morris Water Maze

Although extensive investigation has revealed that an astrocyte-specific protein aquaporin-4 (AQP4) participates in regulating synaptic plasticity and memory, a functional relationship between AQP4 and learning processing has not been clearly established. This study was designed to test our hypothesis that AQP4 modulates the aversive motivation in Morris water maze (MWM). Using hidden platform training, we observed that AQP4 KO mice significantly decreased their swimming velocity compared with wild-type (WT) mice. To test for a relationship between velocities and escape motivation, we removed the platform and subjected a new group of mice similar to the session of hidden platform training. We found that KO mice exhibited a gradual reduction in swimming velocity, while WT mice did not alter their velocity. In the subsequent probe trial, KO mice after no platform training significantly decreased their mean velocity compared with those KO mice after hide platform training. However, all of KO mice were not impaired in their ability to locate a visible, cued escape platform. Our findings, along with a previous report that AQP4 regulates memory consolidation, implicate a novel role for this glial protein in modulating the aversive motivation in spatial learning paradigm.

Association between reduced expression of hippocampal glucocorticoid receptors and cognitive dysfunction in a rat model of traumatic brain injury due to lateral head acceleration

Expression of hippocampal glucocorticoid receptors (GRs) and spatial learning and memory were observed in rat model of diffuse traumatic brain injury (TBI) due to lateral head acceleration with an aim at investigating the relation between GRs expression and cognitive deficits. Immunohistochemical staining, Western blotting, and RT-PCR indicated that down-regulation of GRs expression occurred in the hippocampus among TBI-rats which demonstrated reduced performance of learning and memory in Morris water maze. As the GRs expression bounced up, the cognitive function approached to normal. It is concluded that reduced expression of hippocampal GRs was closely associated with learning and memory deficits in TBI-rats. Hippocampal GRs was involved in the biochemical mechanisms of cognitive deficits after TBI.

Delayed Effects of NMDA Receptor Antagonist MK-801 on Storage and Reconsolidation of Spatial Memory in Rats

We studied the effects of NMDA receptor antagonist MK-801 on the storage and reconsolidation of spatial memory in Morris water maze in adult rats. MK-801 (50 μg/kg) administered 24 h after the completion of training was shown to improve the resistance of spatial memory to spontaneous extinction, while reminder against the background of MK-801 suppresses its ameliorating effect on memory storage. The detected behavioral effects of MK-801 persisted over 60 days after administration and can be associated with its influence on coupled neurogenesis/apoptosis processes induced during memory trace formation in adult animals.

Chronic haloperidol-induced spatial memory deficits accompany the upregulation of D1 and D2 receptors in the caudate putamen of C57BL/6 mouse

AimsHaloperidol (HAL) is an antipsychotic drug that has high affinities to the dopamine D2, but low affinities to D1 receptors in the brain. Of brain regions, caudate putamen (CP) has the highest levels of the D1 and D2 receptors. In this study we evaluated the spatial memory of C57BL/6 mice following chronic administration of HAL and measured levels of D1 and D2 receptors in specific brain regions, with the hypothesis that the D1 and D2 receptors in CP are important players in spatial memory function of the brain. Main methodsC57BL/6 mice received daily intraperitoneal injections of saline or HAL at 1.0 or 2.0mg/kg/day for 3 or 6weeks. Two days after the last injection, spontaneous alternation of mice in a Y-maze was evaluated to measure their exploratory behavior and spatial working memory. The Morris water maze test was performed to measure their spatial learning and memory. D1 and D2 receptors in specific brain regions were measured by Western-blot analysis. Key findingsHAL treatment for 6weeks decreased the spontaneous alternation of mice in Y-maze, altered the acquisition process and impaired spatial memory in Morris water maze. The same treatment increased levels of D1 and D2 receptors in CP and up-regulated D2 receptors in the hippocampus, but did not change the receptors in the prefrontal cortex. SignificanceThese results suggest that the D1 and D2 receptors in CP are among the main targets of HAL and the receptors in CP play an important role in spatial learning and memory.

7,8‐dihydroxyflavone rescues spatial memory and synaptic plasticity in cognitively impaired aged rats

7,8-dihydroxyflavone (7,8-DHF) has recently been identified as a potential TrkB agonist that crosses the blood-brain barrier after i.p. administration. We previously demonstrated that 7,8-DHF in vitro rescues long-term synaptic plasticity in the hippocampus of aged rats. This study assessed the rescue effect of 7,8-DHF in vivo on aging-related cognitive impairment in rats, and further determined whether the effect of 7,8-DHF is age dependent. Aged rats at 22 and 30 months of age were pretested for spatial memory in Morris water maze. The aged-impaired rats were retested twice during 7,8-DHF or vehicle treatment, which started 3 weeks after the completion of the pretest. In the 22-month-old rats, daily i.p. administration of 7,8-DHF for 2 weeks improved spatial memory. The improvement in behavioral tests was associated with increases in synapse formation and facilitation of synaptic plasticity in the hippocampus, as well as the activation of several proteins crucial to synaptic plasticity and memory. A more extended treatment paradigm with 7,8-DHF was required to achieve a significant memory improvement in the severely impaired 30-month-old rats. Moreover, 7,8-DHF moderately facilitated the synaptic plasticity, modified the density but not number of spines in the hippocampus of the oldest rats. Taken together, our results suggest that 7,8-DHF can act in vivo to counteract aging-induced declines in spatial memory and synaptic plasticity and morphological changes of hippocampal neurons. The effect of 7,8-DHF is more pronounced in relatively younger impaired rats than in those of more advanced age. These findings demonstrate the reversal of age-dependent memory impairment by in vivo 7,8-DHF application and support the benefit of early treatment for cognitive aging.

P2‐328: The effect of L‐NAME on Morris water maze memory acquisition consolidation and retrieval

P2‐328: The effect of L‐NAME on Morris water maze memory acquisition consolidation and retrieval

Effects of prenatal irradiation on behaviour and hippocampal neurogenesis in adult rats

Prenatal irradiation is known to have aversive effects on the brain development, manifested in changes in some behavioural parameters in adult individuals. The aim of our work was to assess the effect of prenatal irradiation on different forms of behaviour and on hippocampal neurogenesis in rats. Pregnant female rats were irradiated with a dose of 1 Gy of gamma rays on the 16th day of gravidity. The progeny of irradiated and control animals aged 3 months were tested in Morris water maze (MWM), open field (OF) and in elevated plus maze test (PM). The prenatal irradiation negatively influenced the short-term spatial memory in MWM in female rats, although the long-term memory was not impaired. A statistically significant increase of basic locomotor activity in OF was observed in irradiated rats. The comfort behaviour was not altered. The results of PM showed an increase of anxiety in irradiated females. The level of hippocampal neurogenesis, assessed as the number of cells labelled with 5-bromo-2-deoxyuridine in the area of gyrus dentatus, was not statistically different in irradiated rats. Our results indicate, that prenatal irradiation with a low dose of gamma-rays can affect some innate and learned forms of behaviour in adult rats. We did not confirm a relation of behavioural changes to the changes of hippocampal neurogenesis.