Tehran University Medical Journal

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Background: Diabetes mellitus is a common metabolic disorder accompanied with structural and functional changes in central and peripheral nervous system. Researches showed, memory disturbance were occurred in the course of diabetes. On the other hand, magnesium deficit has been described in diabetic patients. Some researches were showed that, appropriate magnesium supplementation can play a positive role in diabetic control.
Methods: Locally produced male rats were used. Diabetes was induced with intravenous injection of 40 mg/kg streptozotosin. In treatment groups, the animals were received magnesium sulfate via drinking water (10 g/l). Eight weeks after diabetes confirmation, the animals were assessed on Morris Water Maze.
Results: A significant decrease in time of platform finding (latency) and distance of swimming in all four experimental days were seen in all groups. Mean latency in diabetic group was significantly higher than the other. This weak response was almost completely prevented by magnesium sulfate administration.
Conclusion: It seems that after eight weeks magnesium sulfate administration (10g/l), spatial memory of the animals was improved in comparison to diabetic group that can suggest role of magnesium in recovery of diabetic animal memory.

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Background: Many studies have shown that about 45-65% of multiple sclerosis (M.S) patients suffer from cognitive impairments. Semantic memory as one of the subcategories of cognition is quite important for effective communication. In the present study, category-semantic memory was studied in order to evaluate the semantic memory organization in normal individuals and MS patients.

Methods: Ninety voluntaries participated in this study. Participants comprise of 45 MS patients and 45 normal individuals. All participants were matched in terms of age, sex and education. Variables such as the reaction time and the number of correct responses for retrieval (recognition) of natural (animal and fruit) and artifact (object) words were measured in both groups by presentation software. Data analyzed by t-paired and One-Way ANOVA tests. Ethical committee of Tehran University of Medical sciences approved the study.

Results: The results of current study showed significant differences in reaction time and correct responses of artifact and natural categories between the MS and normal individuals (p<0.05). Furthermore, there was significant difference between reaction time and number of correct responses to natural and artifact categories in each group (p<0.05).

Conclusions: This study showed that the organization of semantic categorization as natural and artifact categories is still preserved in multiple sclerosis patients. However, the processing of semantic categorization was different in term of reaction time and number of correct responses between MS patients and normal subjects and the processing of semantic-memory is slower than normal individuals.

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Background: Previous studies suggested that stressful events that release Glucocorticoid from adrenal cortex and also injection of agonists of glucocorticoids receptors probably affect emotional learning and memory process and modulate them. The aim of this study was to determine the effects of acute stress and systemic injection of Corticosterone (as agonist of glucocorticoid receptors) on acquisition (ACQ), consolidation (CONS) and retrieval (RET) of emotional memory in rat.

Methods: In this experimental study we used 180 male Wistar rats (220-250). At the first rats was training in one trial inhibitory avoidance task. On the retention test given 48 h after training, the latency to re-enter the dark compartment of the apparatus (Step-through latency, STL) and the time spent in light chamber (TLC) were recorded during 10 min test. Intraperitoneal corticosterone in doses of 0.5, 1 and 3mg/kg injected 30min before, immediately after instruction and 30min before retrieval test. Also some groups received 10min stressful stimulation by restrainer at the same time. At the end locomotor's activity was measured for all animals.

Results: The data indicated that administration of corticosterone 30min before ACQ (1mg/kg), and immediately after CONS (1, 3mg/kg) enhance and 30min before RET (1, 3mg/kg) impair emotional memory (p<0.05). Acute stress impaired emotional memory in all phases (p<0.05). Also acute stress and injection of Corticosterone have not significantly affect motor activity. 

Conclusions: These findings show that Glucocorticoid receptors in activation dependently plays an important role in modulation of emotional spatial memory processes (ACQ, CONS and RET in new information) for emotional events and these effects varies in different phases.

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Background: Learning and memory are the complicated agents of central nervous system that various regions of brain can be involved in these phenomena, especially regions like hippocamp. Various agents like nitric oxide and morphine can influence learning and memory. About the effects of morphine with other components there was not clear reports so in this study the effect of co-administration of L-Arginine (precursor of nitric oxide) and morphine in hippocampal CA3 area on spatial learning and memory in male rats was investigated.
Methods: Male rats were deeply anaesthetized with ketamine and xylazine and cannula were implanted bilaterally in CA3 of hippocampus by using streotaxic technique, Then male rats were used in seven groups that received saline, L-Arginine (0/3M), L-Arginine (3μg/rat), L-NAME (0/3M), morphine (10mg/rat), L-Arginine (3μg/rat) with morphine or L-NAME with morphine for five days that they were trained in morris water maze to evaluate spatial learning and memory. There was a control group too.
Results: Our results showed that L-Arginine (3μg/rat) improved spatial learning and memory. L-NAME (inhibitor of nitric oxide) decreased spatial learning and memory in male rats. Injection of morphine also decreased spatial learning and memory in male rats. Co-administeration of L-NAME and morphine decreased learning more than morphine individually in male rats.
Conclusion: We concluded that precursor of nitric oxide improved learning and memory in male rats and inhibitor of it and morphine impaired this phenomena and coadministration of inhibitor of nitric oxide and morphine also impaired learning in rats.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Ample evidence indicated that glucocorticoids, when administered after training, enhance memory consolidation in a variety of tasks. The mechanisms underlying the enhancing effects of glucocorticoids on memory consolidation are not well known. The aim of this study was to determine the role of NMDA receptors and calcium channels in glucocorticoid-induced enhancement of avoidance memory consolidation in mice.
Methods: Experiments were performed on 166 male albino mice (about 30gr). The animals were trained in an inhibitory avoidance (IA) task (0.5mA shock for 3 seconds). In Experiment 1, dose- response effects of corticosterone on memory consolidation were determined. Immediately after training in IA task, the animals were received different doses of corticosterone (0.3, 1 or 3mg/kg). In Experiments 2 and 3, effects of corticosterone on memory consolidation were examined in the presence or absence of verapamil, a calcium channel blocker, (2.5, 5 or 20mg/kg) or MK-801, an antagonist of NMDA receptor (0.1mg/kg), respectively. In all experiments, retention test was done two days later.
Results: Results from first experiment revealed that corticosterone at dose of 0.3mg/kg significantly improved consolidation of avoidance. Data from experiments 2 and 3 showed that both verapamil, in doses of 2.5 and 5mg/kg, and MK801 significantly blocked corticosterone-induced enhancement of memory consolidation.
Conclusion: Finding of this study clearly demonstrated that the memory enhancing effects of corticosterone, at least in part mediate via calcium channels and NMDA receptors.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Ascorbic acid improves cognitive impairments in several experimental models. Diabetes causes learning and memory deficits. In this study we hypothesized that chronic treatment with ascorbic acid (100mg/kg, p.o) would affect on the passive avoidance learning (PAL) and memory in control and streptozocin-induced diabetic rats.
Methods: Diabetes was induced by a single i.p. injection of STZ (60mg/kg). The rats were considered diabetic if plasma glucose levels exceeded 250mg/dl on three days after STZ injection. Treatment was begun at the onset of hyperglycemia. PAL was assessed 30 days later. Retention test was done 24 h after training. At the end, animals were weighted and blood samples were drawn for plasma glucose measurement.
Results: Diabetes caused impairment in acquisition and retrieval processes of PAL and memory in rats. Ascorbic acid treatment improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. Ascorbic acid administration also improved the body weight loss and hyperglycemia of diabetics. Hypoglycemic and antioxidant properties of the vitamin may be involved in the memory improving effects of such treatment.
Conclusion: These results show that ascorbic acid administration to rats for 30 days from onset of diabetes alleviated the negative influence of diabetes on learning and memory. Comparing with other nootropic drugs, vitamins have fewer side effects. Therefore, this regimen may provide a new potential alternative for prevention of the impaired cognitive functions associated with diabetes after confirming by clinical trials.

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Background: Cognitive problems in patients with post-traumatic stress disorder (PTSD) include poor concentration and impaired memory. Prevalence of PTSD in all aspects of life is 8% in USA. Regarding the importance of memory in functional levels, this study was performed to review memory status in these patients.

Methods: Fifty male war veterans with PTSD and major depression and 50 male non-veterans with depression participated in this study performed at psychiatric outpatient ward in Baqiyatallah hospital during 2008-2009. The patients met the DSM-IV diagnostic criteria. Depression severity, sex, age, educational level, and marital status were matched in both groups. A psychologist completed demographic and Mississippi questionnaires, PTSD checklist (PCL), beck depression Inventory and wechsler memory scale. The collected data were analyzed using SPSS software (version 11.0). A P-value smaller than 0.05 was considered significant.

Results: The mean age of the veterans and non-veterans was 43.9±4.7 and 42±9.4 years, respectively. Memory status did not differ between the two groups (P>0.05). There was no statistically significant correlation between duration and severity of PTSD with memory impairment (P>0.05). A negative correlation was found between personal and general information with re-experiencing in the veterans (P<0.05). Impaired memory was correlated with age greater than 45, educational level lower than high school diploma, severity of depression and longer participation in war.

Conclusion: Although both PTSD and major depression affected memory, but memory status did not differ between patients with PTSD and depression and patients with chronic depression.

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Background: Diabetes mellitus affects numerous intracellular metabolic processes, which are reflected by changes in the concentration of some plasma constituents. Particularly, the disease may indirectly undermine some functions of the nervous system including learning and memory through altering oxidative stress status. On the other hand, probiotics can enhance the antioxidant capacity. This study was designed to evaluate the effects of probiotics on spatial memory, maze learning and indices of oxidative stress in diabetic rats.
Methods: In this experimental study, 40 male Wistar rats were randomly allocated to 4 groups (n=10 for each): Control (CO), Control probiotic (CP), Control diabetic (DC), and Diabetic probiotic (DP). The probiotic supplement, including Lactobacillus acidophilus, Lactobacillus fermentum, Bifidobacterium lactis (334 mg of each with a CFU of ~1010), was administered through drinking water every 12 hours for 8 weeks. Using morris water maze (MWM), spatial learning and memory were evaluated. Serum insulin and oxidative stress indices, including superoxide dismutase (SOD) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), were measured by standard laboratory kits.
Results: Oral administration of probiotics improved impairment of spatial learning (P=0.008) and consolidated memory (P=0.01) in the rats. Moreover, probiotic treatment increased serum insulin (P<0.0001) and serum superoxide dismutase activity (P=0.007) while it decreased their blood glucose (P=0.006) and 8-OHdG (P<0.0001).
Conclusion: Probiotic supplementation reversed the serum concentrations of insulin and glucose along with an increase in antioxidant capacity in diabetic rats. It also improved spatial learning and memory in the animals. Relevancy of the metabolic changes and behavioral functions need to be further studied.

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Background: Extremely low frequency (0-300 Hz) fields from power lines, electronic equipment and medical devices, have been reported to produce various biological effects. Global system for mobile (GSM) is most largely used in everybody's life. This system utilizes a low frequency band as well as a high frequency range of electromagnetic field. This study investigated the effects of 217 Hz electromagnetic field (the modulating signal in GSM) on spatial learning and memory in rat.
Methods: Twenty four male Wistar rat (200- 250 g) were randomly divided in to three groups as: test, sham and control. Using a Helmholtz coil system, the test group was exposed to a uniform pulsed EMF of 200 µT (micro Tesla) intensity for 4 h/day for 21 days (2 time in a day). This procedure was repeated for the sham group but with no field. All groups were trained prior to the day 21 on the 15th day for five days four trial per day in Morris Water-Maze system. Then the probe test was carried out for 60 seconds with no platform.
Results: The ANOVA test revealed that no significant differences were found between control and exposed rats in all day of learning acquisition. Also, in probe test for investigating the memory, no significant differences observed. (P≤0.05 is accepted for significant level.
Conclusion: This finding is in consistent with previous studies and indicates low frequency band of electromagnetic fields (EMF) (200 µT intensity) in cell phone may not have any effect on the learning acquisition and spatial memory in rat.

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Alzheimer’s disease (AD) is the most prevalent age-related neurodegenerative disorder worldwide, and no cure or prevention has been found for it. Extracellular senile plaque and intracellular neurofibrillary tangles are two important histopathological hallmarks of AD, which are both harmful for the cell. Senile plaques are composed of amyloid beta and neurofibrillary tangles are formed by hyperphosphorylated Tau proteins. In AD, several cellular changes also occur, including oxidative stress, neuroinflammation, accumulation of misfolded proteins, and mitochondrial dysfunction. These events promote neuronal death and finally decline memory and cognition. Lack of success of the available chemical anti-AD therapeutic agents has attracted attention to the concept of the administration of naturally occurring compounds in the treatment of AD. These compounds can be employed as a substitute for the chemical agents or complementary regimens. Several natural products are deemed capable of crossing the blood-brain barrier and are known for their central nervous system-related activity. Among the most important of them are flavonoids. Recent evidence has demonstrated their neuroprotective effects. These plant-derived compounds have strong effects on dementia-induced brain disorders because of their ability to produce antioxidants. Numerous mechanisms have been proposed for flavonoids through which they act for the prevention or recession of the disease process. According to evidence, flavonoids inhibit acetylcholinesterase (AChE), β-secretase (BACE1) and free radicals. They reduce the amyloid-beta toxicity and prevent the formation of neurofibrillary tangles. Also, they help to inhibit apoptosis induced by oxidative stress and neuroinflammation. These products have a role in synaptic plasticity and the generation of new neurons. They can affect various signaling pathways like Extracellular signal-regulated kinase (Erk), Phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK). Overall, these processes can prevent the progression of AD and improve cognitive symptoms. In the present paper, the effect of the most important plant-derived flavonoids is briefly reviewed in different models of AD. The mechanism of action and the important signaling pathways in reducing neuroinflammation, apoptosis, and oxidative damage are discussed. It is concluded that despite the beneficial effect of these compounds, future studies are needed before flavonoids can be used as a drug in the treatment of Alzheimer’s disease.