Effect of caffeine on hippocampal memory and levels of gene expression in social isolation stress.

BACKGROUND: Caffeine (Cf) antagonizes the adenosine receptors and has neuroprotective properties. The effect of Cf has been seen on stress-induced deficits of cognitive. In this study, we have investigated the effect of Cf on learning and memory functions induced by social isolation (SI) stress. MATERIALS AND METHODS: In the present study, 21-day-old Wistar albino male rats (n = 28) were divided into four groups: the control (C), the SI, the Cf, and the social isolation + caffeine (SICf). Cf (0.3 g/L) was added to the drinking water of the experimental animals for 4 weeks. The learning and memory functions were assessed using the Morris Water Maze Test (MWMT). Following, was performed histopathological evaluation and determined hippocampal gene expression levels by RT-qPCR. RESULTS: According to MWMT findings, the time spent in the quadrant where the platform removed was decreased in the SI group compared with the C (p < 0.05). Histological evaluation showed morphological changes in SI by irregular appearance, cellular edema, and dark pycnotic appearance of nuclei in some neurons. However, it was observed that the histological structure of most of the neurons in the SICf group was similar to the C and Cf groups. Hippocampal SNAP25 expression was decreased in the Cf and SICf groups than in the C group (p < 0.05). The GFAP expression was increased in the SICf group than in the C group (p < 0.05). NR2A increased in the SI and SICf groups compared with C and Cf groups (p < 0.05). NR2B expression decreased in the Cf group compared with C and SI groups (p < 0.05). CONCLUSIONS: SI impaired spatial memory and causes morphological changes in adolescent rats, but this effect of isolation was not seen in Cf-treated animals. The effects of SI on NR2A, Cf on NR2B, and SNAP25 are remarkable. Here, we propose that the impaired effect of SI on spatial memory may be mediated by NR2A, but further studies are needed to explain this effect.

The roles of long non-coding RNAs in the necroptotic signaling of colon cancer cells.

BACKGROUND: Necroptosis is a controlled form of necrosis which can be stimulated in cases where the apoptosis signal is absent. Necroptosis can be induced by DR family ligands and by various intracellular and extracellular stimuli that triggers the activation of DR family ligands. Necrostatins, which are specific RIP1 antagonists, prevent necroptosis by inhibiting RIP1 kinase, allowing survival and propagation of cells in the presence of DR ligands. Furthermore, there is a mounting evidence that long non-coding RNA (lncRNA) molecules accomplish vital functions in cell death processes such as apoptosis, autophagy, pyroptosis, and necroptosis. Accordingly, here we aimed to decipher the lncRNAs that are involved in the control and maintenance of necroptosis signaling. METHODS AND RESULTS: Colon cancer cell lines, HT-29 and HCT-116 were used for the study. For the chemical modulation of necroptosis signaling, 5-Fluorouracil, TNF-α and/or Necrostatin-1 were used. Gene expression levels were determined by quantitative real-time PCR. Remarkably, lncRNA P50-associated COX-2 extragenic RNA (PACER) was identified to be suppressed in necroptosis-induced colon cancers, whereas the expression of PACER was restored when necroptosis was suppressed. In addition, no detectable change was observed in HCT-116 colon cancer cells, as these cells lack the expression of RIP3 kinase. CONCLUSIONS: Collectively, current findings clearly imply that PACER have key regulatory roles in the control of necroptotic cell death signaling circuitry. Notably, the tumor promoter activity of PACER might be responsible for the lack of necroptotic death signal in cancer cells. Also, RIP3 kinase seems to be essential component in PACER-associated necroptosis.

miR-19a and miR-421 target PCA3 long non-coding RNA and restore PRUNE2 tumor suppressor activity in prostate cancer.

BACKGROUND: Prostate cancer antigen 3 (PCA3) is the most promising diagnostic biomarker for the differential diagnosis of prostate cancer identified to date. As a dominant-negative oncogene, PCA3 negatively regulates the expression of tumor suppressor PRUNE2 (a human homolog of the Drosophila prune gene) gene. Although interaction between PCA3-PRUNE2 was clearly reported, the precise mechanism how PCA3 is upregulated in prostate cancer remained highly elusive. Accordingly, here we aimed demonstrate the role of microRNAs in PCA3 upregulation and interplay between these miRNAs and PCA3-PRUNE2 axis. METHODS AND RESULTS: We evaluated expression of PCA3, PRUNE2 and miRNAs by quantitative reverse transcription polymerase chain reaction. Overexpression and silencing of miRNAs were achieved by synthetic miRNA mimics and inhibitors, respectively. Colony formation, migration, apoptosis, and cell cycle assays were performed to reveal the effects of miRNA modulation. We identified that PCA3 expression was significantly downregulated in both prostate cancer tissues and cells and inversely correlated with the expressions of miR-19a and miR-421. Restoring the functions of miR-19a and miR-421 by miRNA mimics significantly downregulated the expression of PCA3 and promoted apoptosis and cell cycle blockade and interfered with the proliferation and migration in prostate cancer cells. Conversely, silencing the expressions of these miRNAs yielded the opposite effect. CONCLUSIONS: Collectively, our results uncover a previously unrecognized novel mechanism on PCA3 upregulation in prostate cancer and proved that miR-19a and miR-421 might be responsible for the increased expression of PCA3, indicating that both miRNAs might be novel candidates for prostate cancer diagnosis and therapy.

Living with female rats exposed to restraint stress during pregnancy caused depressive-like behavior in male rats and stress-induced apoptosis.

OBJECTIVE: Maternal mood disorders such as postpartum depression (PPD) can negatively affect the lives not only of mothers but also of partners. The purpose of this study investigates emotional behavior and hippocampal apoptosis alterations of the male live with a postpartum depressed female. METHODS: Pregnant rats in the stress group were exposed to restraint stress (RS). The male rats who shared the same cages were not exposed to RS. To explain the consequences of depressive-like behavior and anxiety, animals were exposed to the forced swim test (FST), open-field test (OFT), and elevated plus maze (EPM). The apoptotic cell number was detected by terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP biotin nick-end labeling (TUNEL) staining. RESULTS: According to FST, PPD caused more immobility, reduced swimming, and climbing compared to control groups in the stressed female and male (p < 0.05). For the crossing number of squares in the center area, the main effect of the group was significant (p < 0.05). Stressed groups have a higher crossing number of squares in the center area compared to control groups. In the OFT, there was a significant increase in the time spent in the center area in the stress female and male group compared to the control female and male group (p < 0.05). For the EPM, time spent in the close arms was increased in the control male and stress male compared to the stress female group (p < 0.05). Female and male rats with PPD demonstrated apoptosis in neuron and glial cells in the hippocampus. CONCLUSIONS: The present study demonstrates that RS results in PPD in females. Furthermore, it implicates RS as a potential risk factor for the development of postpartum mood disorder in males. Most of the studies on paternal PPD have been done by using self-report questionnaires. Studies on physiological and hormonal changes during the postpartum period among fathers would provide information on biological factors of depression.

Investigation of the effect of training on serotonin, melatonin and hematologic parameters in adolescent basketball players.

OBJECTIVES: Exercise can improve both health and mood. Some beneficial effects of exercise are attributed to endocrine status. This study aims to evaluate the effect of eight weeks of basketball training on melatonin, serotonin, and hematologic parameters in basketball players. METHODS: The experimental group was selected form 34 healthy young boys, aged between 13 and 16 years old. The participants were randomly assigned to the control group (n=17) and the exercise group (n=17). The exercise program consisted of 2 h/day aerobic activity of basketball training in 5 days a week for 8 weeks. Venous blood was taken on the day before experiment (pre-exercise) and on the day following the last exercise (post-exercise) and hormone levels were detected by ELISA. RESULTS: Serotonin and melatonin levels significantly increased in the post-exercise group compared to the other groups (p<0.05). Exercise caused increase in WBC, RBC, HCT and Hb levels (p<0.05) while did not alter PLT, MCH, and PCT levels (p>0.05). This study indicates that an eight weeks-long regular aerobic exercise increased melatonin and serotonin levels, and also altered some hematological parameters. CONCLUSIONS: In conclusion, it is believed that improvement in levels of serotonin, melatonin, and hematological parameters after eight weeks of regular basketball training in basketball players could be attributed to beneficial effects of exercise. Investigation in other branches of sports and in different gender and age groups would make contribution into exercise physiology and training science.

Mild regular treadmill exercise ameliorated the detrimental effects of acute sleep deprivation on spatial memory.

Vulnerable areas like the hippocampus are sensitive to insults such as sleep deprivation (SD); they are also susceptible to environmental enrichment. Much evidence is accumulating that chronic sleep deprivation causes alterations in the hippocampus that responsible for spatial memory. However, there is conflicting about the differences between acute and chronic SD results. The purpose of this study was to determine the protective effects of mild treadmill exercise on acute SD rats. Four groups were created as control, exercise, sleep deprivation, exercise + sleep deprivation. Multiple platforms method was used to induce REM sleep deprivation (RD) for 48 h. The exercise was applied fivedaysperweekforfour weeks(5 × 4). For the first and second weeks, the length of the exercise was 15 min in two sessions (5 min interval) followed by 15 min in three, 15 min in four sessions. Morris water maze (MWM) was used as a spatial memory test. Gene level was determined by using the qPCR technique. Malondialdehyde (MDA) content in the hippocampus was measured as an extent of peroxidative damage to lipids by using the ELISA method. 48 h RD impaired long-term spatial memory significantly. Mild, regular treadmill exercise ameliorated the detrimental effects of acute sleep deprivation on memory. There was no significant difference in MDA between groups. Hippocampal gene expression did not show any changes in all groups. Lack of correlation between memory impairment and levels of genes in the hippocampus is likely to be related to the differences in behavioral and genetic mechanisms.

Evaluation of effects of a modified asymmetric rapid maxillary expansion appliance on the upper airway volume by cone beam computed tomography.

BACKGROUND/PURPOSE: The rapid maxillary expansion is accepted as the gold standard for the treatment of unilateral posterior crossbite in growing children. This study used cone beam computed tomography (CBCT) to evaluate the effects of a modified asymmetric rapid maxillary expansion (ARME) appliance on the upper airway volumes. MATERIALS AND METHODS: A modified ARME appliance was used on 12 adolescent male patients (mean age: 13.92 ±â€¯0.82 years) with a class I skeletal relationship and posterior unilateral crossbite. Lateral cephalometric measurements and upper airway volume were evaluated using CBCT images. The posterior airway volumes of the oropharyngeal and nasopharyngeal airways were measured. RESULTS: Cephalometric measurements showed significant (P < 0.05) posterior rotation of the mandible. There was no significant movement of the maxilla according to the cranial base on the sagittal plane. Nasopharyngeal and oropharyngeal airway volumes increased significantly (P < 0.05). CONCLUSION: The results of this study demonstrate that treatment with the modified ARME has no significant effect on the maxilla but may increase the upper airway volume.

Associations of apelin, leptin, irisin, ghrelin, insulin, glucose levels, and lipid parameters with physical activity during eight weeks of regular exercise training.

OBJECTIVES: This study aims to evaluate the effects of 8 weeks of basketball training on apelin, leptin, irisin, ghrelin, insulin, glucose, and blood lipids among basketball players. METHODS: The exercise groups were given 2 h of basketball training for 5 d a week and for 8 weeks. The control group was randomly selected among the adolescents who did not regularly exercise. RESULTS: The apelin and ghrelin levels significantly increased; however, leptin, irisin, and insulin levels statistically decreased in the post-exercise group compared to the other groups (p < .05). The results suggest low levels of cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) parameters (p < .05). CONCLUSIONS: This study demonstrated that after 8 weeks of chronic exercise training, apelin and ghrelin levels increased; in contrast, leptin, irisin, and insulin levels decreased. The decrease in leptin and irisin levels is compatible with the pattern of decrease in the lipid levels as a result of chronic exercise.

The role of toll-like receptors in the protective effect of melatonin against doxorubicin-induced pancreatic beta cell toxicity.

AIMS: Doxorubicin, an anticancer drug, has a toxic effect on many tissues such as heart, pancreas, liver, kidney, and testis. The aim of current study is to investigate whether melatonin would be protective in doxorubicin-induced beta (ß) cell toxicity via HMGB1/TLR2/TLR4/MAPK/NF-қB signaling pathway. MAIN METHODS: Human pancreatic ß cell (1.1B4) was used in the present study. Four experimental groups were created as control, melatonin (10 µM), doxorubicin (2 µM) and the combination of melatonin with doxorubicin. Following 24-h treatment, Mitogen-activated protein kinase (MAPKs), Toll like receptors (TLRs) including TLR2 and TLR4, pro-and anti-apoptotic protein expression levels were determined by western blotting. Total antioxidant (TAS), oxidant status (TOS) and oxidative stress index (OSI) of the cells as well as superoxide dismutase (SOD) levels were determined. Active caspase-8 activity was measured and TUNEL staining was performed to study apoptotic pathways. Mitochondrial membrane potential (MMP), some protein expressions and F-actin distribution were analyzed. KEY FINDINGS: Doxorubicin caused to depolarize MMP, resulting in enhancing apoptosis by activation of caspase-8 via MAPKs/NF-кB pathway via elevation of TOS and decreasing TAS. Also, doxorubicin destroyed F-actin distribution and elevated TLR2 and some apoptotic proteins, including Bax. However, co-treatment of melatonin with doxorubicin could reverse depolarization of MMP and inhibition of apoptosis through MAPK/NF-кB signaling by decreasing TOS and increasing TAS. The co-treatment reversed the alternations of TLR2, TLR4, MAPKs and apoptotic protein expressions induced by doxorubicin. SIGNIFICANCE: Melatonin could be a good candidate against pancreatic ß cell toxicity-induced by doxorubicin through TLR2/TLR4/MAPK/NF-кB pathways.

Caffeine as a potential arousal enhancer: altered NMDA subunit gene expression without improving cognitive performance in REM sleep deprived rats.

Caffeine is one of the most extensively consumed stimulants in the world and has been suggested to induce wakefulness by antagonizing the function of the adenosine A2A receptor. Therefore, we investigated the effects of chronic caffeine consumption on learning and memory in the REM sleep-deprived rats.Male Wistar rats (n = 50), were randomly assigned into 5 groups: Control (C), Caffeine (Cf), Pedestal Control (PC), Sleep Deprivation (SD), Sleep Deprivation and Caffeine (SD + Cf). Sleep deprivation procedure was applied as the flower-pot technique. SD and SD + Cf groups were deprived for 18 hours in a day for 21 days. Caffeine was administered daily in drinking water (0.3 g/L) for 5 weeks. For evaluated learning and memory function, Morris Water Maze Test (MWM) was used. Fluidigm Access Array was used for Grin2a, Grin2b, BDNF, cdk5/cdk5r1, CaMKIIa genes expression in the hippocampus. Distance moved and escape latency were decreased through trial days (p<0.05). However, there is no significant difference between groups for time spent in targeted quadrant during probe test for memory performance. Grin2a up-regulation was found in Cf and SD+Cf (p<0.05), and cdk5r1 increased in Cf and PC control (p<0.05). Also, BDNF up-regulation was found in PC group. Grin2b, Cdk5, CaMKIIa expression levels were not changed significantly. We showed chronic caffeine altered some of the hippocampal genes without changing learning and memory in REM sleep deprived rats. Chronic consumption of caffeine caused up-regulation in Grin2a that subunit of NMDA receptor. We supposed that chronic caffeine consumption maintained arousal without affecting learning and memory performance.

Effects of different loading exercises on apelin levels and physical and hematologic parameters of swimmers.

Background The purpose of this study was to investigate the effects of different exercise loads (short, medium and long swimming distances) on apelin levels and some physical and hematologic parameters of male professional swimmers. Materials and methods Apelin levels, hematologic parameters, whole blood values and physical measurements, including body mass index (BMI), aerobic power values and anaerobic power values, were also obtained. Results It was determined that the thrombocyte, erythrocyte and leukocyte values from the hematologic parameters increased after exercise (p < 0.05). According to the results, there were significant differences (p < 0.05) between the pretest apelin level (2090.75 pg/mg) and the apelin levels taken after swimming M 200 m (4260.43 pg/mg) and after swimming L 400 m (3694.4 pg/mg). Conclusions The different exercise loads had significant effects on the hematologic parameters and apelin values in the swimmers. The study also determined the relationships between swimming exercises and aerobic and anaerobic capacity and BMI.

The Effects of Using Plaque-Disclosing Tablets on the Removal of Plaque and Gingival Status of Orthodontic Patients.

OBJECTIVE: The aim of this study was to investigate the effects of using plaque-disclosing tablets (PDTs) on the plaque and gingival index scores of patients wearing fixed orthodontic appliances. METHODS: In group A (n=16), the subjects were motivated by conventional oral hygiene instructions, including verbal information about tooth brushing. The patients in group B (n=17) were motivated using PDTs used in the dentists' office to show the locations of biofilms in addition to the instructions given to group A. Both the chairside demonstration performed in group B and the at-home use of disclosing tablets were undertaken by those in group C (n=15). The periodontal parameters were recorded before applying the fixed appliance (T0) and after the first (T1) and third (T2) months. RESULTS: The plaque index (PI) scores of group C were significantly lower (p<0.05), when compared to groups A and B, after the first (T1) and third months (T2); however, no significant differences (p>0.05) were found between groups A and B. The gingival status of group C did not change significantly (p>0.05) over the three months and was statistically lower when compared to groups A and B. CONCLUSION: The use of PDTs at home may enhance the plaque removal efficiency and gingival health stability, by facilitating self-examination.

Effects of different exercise loads on the thyroid hormone levels and serum lipid profile in swimmers.

Background The aim of this study was to investigate the effects of different exercise loads (short, medium and long swimming distances) on the thyroid hormone (THs) levels and serum lipid profiles of male professional swimmers. Materials and methods The participants in this study were 20 healthy male professional swimmers aged 18-22 years, who all competed at an elite level. The THs levels [thyroid-stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4)] and serum lipid profile were also obtained. Results It was determined that the TSH and T4 values increased after exercise (p < 0.05). When compared to the pretest values, the increase in the TSH and T4 values following the L400 tests was statistically significant (p < 0.001 and p < 0.05). It was also determined that the changes in the cholesterol, high-density lipoprotein (HDL) and total glucose (TG) values were significant after exercise (p < 0.001). There was no significant difference between the groups in terms of the low-density lipoprotein (LDL) values (p = 0.07). According to the results, the cholesterol counts for the M200 and L400 groups were lower than the pretest counts (p < 0.001). When compared to the pretest values, the decrease in the HDL counts for the M200 and L400 groups was higher than the pretest HDL counts (p < 0.001 and p < 0.05, respectively). Further, the triglycerides counts for the M200 and L400 groups were higher than the pretest counts (p < 0.001). Conclusions Different exercise loads can have a positive impact on the physical health of swimmers via their lipid profiles and THs. Additionally, swimming exercise could be considered an efficient protective strategy against metabolic disorders, as it serves to balance the serum lipid levels.

Protective Effect of Quercetin Against Oxidative Stress-induced Toxicity Associated With Doxorubicin and Cyclophosphamide in Rat Kidney and Liver Tissue.

INTRODUCTION: Doxorubicin and cyclophosphamide are widely used anticancer drugs with substantial toxicity in noncancerous tissue resulting from oxidative damage. Quercetin is a potent antioxidant compound. We hypothesized that quercetin administration would ameliorate the toxic effects of doxorubicin and cyclophosphamide prior to pregnancy. MATERIALS AND METHODS: Cyclophosphamide, 27 mg/kg, and doxorubicin, 1.8 mg/kg, were administered to rats as intraperitoneal doses once every 3 weeks for a total of 10 weeks with or without concurrent treatment with quercetin, 10 mg/kg/d. Oxidative stress parameters were evaluated in maternal kidney and liver tissues after gestation. RESULTS: Doxorubicin was associated with elevated kidney tissue malondialdehyde relative to the controls and quercetin only treatment (P < .05). Both cyclophosphamide and doxorubicin were associated with elevated malondialdehyde levels in the liver tissue (P < .05). Doxorubicin treatment was associated with decreased liver glutathione peroxidase (P < .05). Quercetin treatment suppressed the accumulation of malondialdehyde and increased glutathione peroxidase levels during doxorubicin and cyclophosphamide treatment (P <.05) Conclusions. Treatment with quercetin in patients receiving doxorubicin and cyclophosphamide results in therapeutic restoration of homeostatic expression of the antioxidant parameters, reducing oxidative damage to the liver and kidney.

Mechanisms of Alzheimer's Disease Pathogenesis and Prevention: The Brain, Neural Pathology, N-methyl-D-aspartate Receptors, Tau Protein and Other Risk Factors.

The characteristic features of Alzheimer's disease (AD) are the appearance of extracellular amyloid-beta (Aß) plaques and neurofibrillary tangles in the intracellular environment, neuronal death and the loss of synapses, all of which contribute to cognitive decline in a progressive manner. A number of hypotheses have been advanced to explain AD. Abnormal tau phosphorylation may contribute to the formation of abnormal neurofibrillary structures. Many different structures are susceptible to AD, including the reticular formation, the nuclei in the brain stem (e.g., raphe nucleus), thalamus, hypothalamus, locus ceruleus, amygdala, substantia nigra, striatum, and claustrum. Excitotoxicity results from continuous, low-level activation of N-methyl-D-aspartate (NMDA) receptors. Premature synaptotoxicity, changes in neurotransmitter expression, neurophils loss, accumulation of amyloid ß-protein deposits (amyloid/senile plaques), and neuronal loss and brain atrophy are all associated with stages of AD progression. Several recent studies have examined the relationship between Aß and NMDA receptors. Aß-induced spine loss is associated with a decrease in glutamate receptors and is dependent upon the calcium-dependent phosphatase calcineurin, which has also been linked to long-term depression.

Enriched environment has limited capacity for the correction of hippocampal memory-dependent schizoid behaviors in rats with early postnatal NMDAR dysfunction.

Pre- and early postnatal stress can cause dysfunction of the N-methyl-d-aspartate receptor (NMDAR) and thereby promote the development of hippocampus memory-dependent schizoid abnormalities of navigation in space, time, and knowledge. An enriched environment improves mental abilities in humans and animals. Whether an enriched environment can prevent the development of schizoid symptoms induced by neonatal NMDAR dysfunction was the central question of our paper. The experimental animals were Wistar rats. Early postnatal NMDAR dysfunction was created by systemic treatment of rat pups with the NMDAR antagonist MK-801 at PD10-20 days. During the development period (PD21-90 days), the rats were reared in cognitively and physically enriched cages. Adult age rats were tested on navigation based on pattern separation and episodic memory in the open field and on auto-hetero-associations based on episodic and semantic memory in a step-through passive avoidance task. The results showed that postnatal NMDAR antagonism caused abnormal behaviors in both tests. An enriched environment prevented deficits in the development of navigation in space based on pattern separation and hetero-associations based on semantic memory. However, an enriched environment was unable to rescue navigation in space and auto-associations based on episodic memory. These data may contribute to the understanding that an enriched environment has a limited capacity for therapeutic interventions in protecting the development of schizoid syndromes in children and adolescents.

Effects of NMDA receptor blockade during the early development period on the retest performance of adult Wistar rats in the elevated plus maze.

The elevated plus maze (EPM) is an animal model of anxiety used to test the effects of anxioselective drugs. The loss of the anxiolytic effect of drugs during the second exposure to the EPM is called the "one trial tolerance" (OTT) phenomenon. The present study was designed to investigate the relationship between the OTT phenomenon and N-methyl-D-aspartate (NMDA) receptor blockade in the early developmental period of rats. NMDA receptor blockade was accomplished using MK-801 treatment given between postnatal days 20-30. Beginning on postnatal day 20, the rats were subcutaneously injected with MK-801 twice a day at the nape of the neck for a period of 10 days (0.25 mg/kg). Increased open arm exploration was observed in MK-801-treated rats during trial 1 (p = 0.001) and trial 2 (p = 0.003). The rats spent less time in the closed arms as compared to the saline animals in trial 1 (p = 0.006), and this time decreased further in trial 2 (p = 0.02). The fecal boli of the MK-801 group was decreased in trial 1 as compared to the saline group (p = 0.01), but was not significantly different in trial 2 (p = 0.08). In conclusion, NMDA receptor blockade using MK-801 produced an anxiolytic-like effect in trials 1 and 2. Furthermore, OTT was not affected by NMDA receptor blockade.

The effects of N-Methyl-D-Aspartate receptor blockade during the early neurodevelopmental period on emotional behaviors and cognitive functions of adolescent Wistar rats.

The N-Methyl-D-Aspartate (NMDA) receptor is expressed abundantly in the brain and plays an important role in neuronal development, learning and memory, neurodegenerative diseases, and neurogenesis. In this study, we evaluated the effects of NMDA receptor blockade during the early neurodevelopmental period on exploratory locomotion, anxiety-like behaviors and cognitive functions of adolescent Wistar rats. NMDA receptor hypofunction was induced 7-10 days after birth using MK-801 in rats (0.25 mg/kg twice a day for 4 days via intraperitoneal injection). The open-field (OF), elevated plus maze (EPM) and passive avoidance (PA) tests were used to evaluate exploratory locomotion, anxiety-like behaviors and cognitive functions. In the OF test, MK-801 caused an increase in locomotion behavior (p < 0.01) and in the frequency of rearing (p < 0.05). In the EPM test, MK-801 treatment increased the time spent in the open arms, the number of open arm entries and the amount of head dipping (p < 0.01). MK-801 treatment caused no statistical difference compared to the control group in the PA test (p > 0.05). Chronic NMDA receptor blockade during the critical period of maturation for the glutamatergic brain system (postnatal days 7-10) produces locomotor hyperactivity and decreased anxiety levels, but has no significant main effect on cognitive function during adolescence.

The investigation of neonatal MK-801 administration and physical environmental enrichment on emotional and cognitive functions in adult Balb/c mice.

N-methyl-D-aspartate (NMDA) receptors play an important role in brain maturation and developmental processes. It is known that growing up in an enriched environment has effects on emotional and cognitive performance. In our study, we evaluated the effects of physically enriched environment on the emotional and cognitive functions of the adult brain in the setting of previous NMDA receptor hypoactivity during the critical developmental period of the nervous system. In this study, NMDA receptor blockade was induced 5-10 days postnatally (PD5-10) using MK-801 in mice Balb/c (twice a day 0.25 mg/kg, for 5 days, intraperitoneal). MK-801 was given to developing mice living in a standard (SE) and an enrichment environment (EE) and once the animals reached adulthood, emotional behaviors were evaluated using an open field test (OF) and an elevated plus maze (EPM) test whereas cognitive processes were evaluated using the Morris water-maze (MWM). The EE group showed decreased locomotor activity (p<0.05) in the OF and increased exploratory behaviour (p<0.01) and decreased fear of heights/anxiety-like behaviour (p<0.05) in the EPM test. The EE had positive effects on spatial learning in the MWM (p<0.05). Blockade of the NMDA receptor increased the fear of height (p<0.05), decreased exploratory behaviour and locomotor activity (p<0.001). Also, it led to decreased spatial learning (p<0.05). The decreases in spatial learning and exploratory behaviours and the increase in fear of heights/anxiety-like behaviour with NMDA receptor blockade was not reversed by EE. NMDA receptor blockade during the critical period of development led to deterioration in the emotional and cognitive processes during adulthood. An enriched environmental did not reverse the deleterious effects of the NMDA receptor blockade on emotional and cognitive functions.

The effect of neonatal N-methyl-D-aspartate receptor blockade on exploratory and anxiety-like behaviors in adult BALB/c and C57BL/6 mice.

N-methyl-D-aspartate (NMDA) receptors play an important role in brain maturation and developmental processes. In our study, we evaluated the effects of neonatal NMDA receptor blockade on exploratory locomotion and anxiety-like behaviors of adult BALB/c and C57BL/6 mice. In this study, NMDA receptor hypofunction was induced 7-10 days after birth using MK-801 in BALB/c and C57BL/6 mice (0.25mg/kg twice a day for 4 days via intraperitoneal injection). The open-field (OF) and elevated plus maze (EPM) tests were used to evaluate exploratory locomotion and anxiety-like behaviors. In the OF, BALB/c mice spent less time in the center of the field (p<0.05) and had less vertical locomotor activity (p<0.01) compared to C57BL/6 mice. In BALB/c mice, MK-801 caused a decrease in vertical and horizontal locomotor activity in the OF test, compared to the control group (p<0.05). In C57BL/6 mice, MK-801 treatment increased horizontal locomotor activity and decreased time spent in the center in the OF test (p<0.05). In the EPM, the number of open-arm entries, the percentage of open-arm time (p<0.01) and total arm entries (p<0.05) were lower in BALB/c mice compared to C57BL/6 mice. In BALB/c mice, MK-801 caused an increase in the percentage of open-arm time compared to the control group (p<0.05). In C57BL/6 mice, MK-801 caused a decrease in the percentage of open-arm time compared to the control group (p<0.05). MK-801 decreased exploratory and anxiety-like behaviors in BALB/c mice. In contrast, MK-801 increased exploratory and anxiety-like behaviors in C57BL/6 mice. In conclusion, hereditary factors may play an important role in neonatal NMDA receptor blockade-induced responses.