Kubra Akillioglu

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.

Effect of ketamine on exploratory behaviour in BALB/C and C57BL/6 mice

In this study, we evaluated the effect of ketamine on exploratory locomotion behaviours in the Balb/c and C57BL/6 strains of mice, which differ in their locomotion behaviours. Intraperitoneal administration of ketamine at three different doses (1, 5 or 10 mg/kg, 0.1 ml/10 gr body weight) was performed on adult male Balb/c and C57BL/6 mice. The same volume of saline was applied to the control group. The open-field and elevated plus maze apparatus were used to evaluate exploratory locomotion. In the open-field test, Balb/c mice less spend time in the centre of the field and was decreased locomotor activity compared to C57BL/6 mice (p<0.01). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in locomotor activity and an increase in the amount of time spent in the centre in the open-field test, compared to the control group (p<0.05). In C57BL/6 mice, ketamine treatment (1 and 10 mg/kg) decreased locomotor activity (p<0.05). In C57BL/6 mice, the three different doses of ketamine application each caused a decrease in the frequency of centre crossing (p<0.001) and the spent time in the centre (p<0.05). In the elevated plus maze, the number of open-arm entries, the percentage of open-arm time and total arm entries were decreased in Balb/c mice compared to C57BL/6 mice (p<0.001). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in the open-arm activity (p<0.001). Ketamine application (10 mg/kg) decreased the open-arm activity in C57BL/6 mice (p<0.05). A subanaesthetic dose of ketamine increased exploratory locomotion in Balb/c mice. In contrast, a subanaesthetic dose of ketamine decreased exploratory locomotion in C57BL/6 mice. In conclusion, hereditary factors may play an important role in ketamine-induced responses.

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.

Environmental enrichment does not reverse the effects of maternal deprivation on NMDAR and Balb/c mice behaviors

Early adverse life experiences have been associated with anxiety-like behavior and memory impairment. N-methyl-d-aspartate receptors (NMDARs) play an important role in brain development. Enriched environments are known to positively influence emotional and cognitive functions in the brain. We examined the effects of maternal deprivation (MD) on NMDAR subunits in the hippocampus, locomotor activity, anxiety behaviors, and learning-memory performance of Balb/c mice. We also examined whether these effects could be reversed by raising the offspring in an enriched environment. The mice were separated from their mothers for a single 24h episode on postnatal day (PND) 9. The mice were weaned on day 21 and were housed under either standard (SE) or enriched (EE) environmental conditions. Emotional behaviors and cognitive processes of mice were evaluated using an open field (OF) test, an elevated plus maze (EPM) test, and a Morris water-maze (MWM). NMDAR subunits (GluN1, GluN2A, and GluN2B) mRNA expression levels in the hippocampus were examined by real-time PCR. In OF, MD had no effect on horizontal locomotor activity. MD increased anxiety-like behaviors in the EPM and decreased spatial learning performance in MWM; however, these effects were not reversed by EE. MD (in SE and EE conditions) increased GluN1, GluN2A, and GluN2B mRNA expressions in the hippocampus. In conclusion, MD led to the deterioration of the emotional and cognitive processes during adulthood. Moreover, environmental enrichment did not reverse the deleterious effects of the MD on emotional and cognitive functions and increased the NMDAR levels.

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.

The effect of 900 and 1800 MHz GSM-like radiofrequency irradiation and nicotine sulfate administration on the embryonic development of Xenopus laevis

The aim of this study was to investigate the effects of GSM-like radiofrequency electromagnetic radiation (RF EMR) and nicotine sulfate (NS) exposure on Xenopus embryonic development.The developmental effects of GSM-like RF-EMR (900-1800 MHz, at a SAR value of 1W/kg and NS on Xenopus laevis embryos were investigated). Following the application of radiofrequency radiation and/or NS administration, the embryos were closely examined in order to determine their possible teratogenic effects. Xenopus frogs obtained from the Department of Physiology of the Cukurova University, in accordance described by the Standard Guide of the American Society for Testing and Materials (ASTM). Following the exposure of Xenopus embryos to RF-EMR at 900 and 1800 MHz (1.0W/kg) for 4, 6 and 8h; the whole body specific energy absorption rate (SAR) of the embryos was calculated. With the exception of irradiation at 1800 MHz no dramatic developmental anomalies were observed in the Xenopus embryos in association with RF-EMR applications. Combined RF-EMR and NS applications resulted in dramatic abnormalities and death among the Xenopus embryos. The study results indicated that GSM-like RF-EMR (e.g. radiation from cell phones) was not as harmful to Xenopus embryos as might have been expected. However, the combined effects of GSM-like RF-EMR and NS on Xenopus embryos were more severe than the effect of RF-EMR or NS alone. In conclusion, the study results appear to suggest that the combined use of nicotine and cell phones might result in more pronounced detrimental effects on the health of smokers.

Evaluating the Teratogenicity of Ritodrine and Nifedipine using a Frog Embryo Teratogenesis assay (FETAX).

Abstract The Frog Embryo Teratogenesis Assay—Xenopus (FETAX) was used to assess the teratogenic potential of two tocolytics. Embryos of the South African clawed frog, Xenopus laevis, were exposed to ritodrine or nifedipine. Exposure media were changed and monitored at 24-hour intervals. The 96-hour LC50 (Lethal concentration), the 96-hour EC50 (Malformation), and the No Observable Adverse Effect Concentrations (NOAEC) and the Lowest Observable Adverse Effect Concentration (LOAEC) for mortality, malformation and length were determined for each drug. Nifedipine was determined to be the more toxic and teratogenic than ritodrine, with a LC50 of 0.606 µg/L, an EC50 of 0.006 µg/L, and a teratogenicity Index (TI) value (LC50/EC50) of 101. On the other hand, the LC50 of ritodrine was 28.571 mg/L. In addition; the LC50, EC50 and TI values for nifedipine in the 5 mg/L ritodrine + nifedipine combination group were determined as 1.050 µg/L, 0.868 µg/L and 1.5 respectively. For ritodrine, the NOAEC and LOAEC values were determined as 2 mg/L and 4 mg/L, respectively. For the nifedipine and the ritodrine + nifedipine groups; while the LOAEC values of these groups were 0.0001 µg/L and 0.1 µg/L, respectively. NOAEC value couldn’t be determined. Our results demonstrated that nifedipine administration was associated with higher levels of teratogenic and toxic effects. However, the ritodrine + nifedipine combination form reduced the toxic and teratogenic effects of nifedipine on Xenopus embryos. Further studies should be conducted in order to investigate the optimal combination concentrations of these substances for the treatment of preterm labor.

Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801

Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (p<0.05), while the open-field test indicated a decrease in locomotor activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not reverse impairment in the locomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.

A comparative study on the influence of estrous cycle on cognitive and coping behaviors in rats

Materials and methods The present study was investigate the influence of estrous cycle in adult female Wistar rats on the responses to emergency novelty by using an open field (OF) and on the recognition of fearful partial or whole cues presented during testing in the passive avoidance (PA) apparatus. In conditioning task, rats recieved a single shock (1 mA) following a 30-s preshock exposure period to the shock associated context of the PA. Estrous cycle phases were determined by vaginal lavage.

Diyabetik Hayvan Modelleri ve Önemi

Diabetes mellitus gunumuzde sikligi, sebep oldugu komplikasyonlar ve tedavi maliyeti nedeniyle tum dunyada onemi gittikce artan bir saglik problemi olarak karsimiza cikmaktadir. Diger bilimsel calismalarda oldugu gibi diyabet arastirmalarinda da cesitli hayvan modelleri kullanilmaktadir. Tip 1 ve tip 2 diabet patolojisinin altinda yatan mekanizmalari ortaya cikarmak, komplikasyonlarini onlemek ve yeni ilac denemeleri icin deneysel hayvan modelleri gelistirilmektedir. Bircok hayvan turunde kimyasal bazi ilaclarla (streptozotosin ve alloksan), cerrahi olarak pankreasin cikarilmasiyla (pankreatektomi) ve genetik yontemlerle tip 1 ve tip 2 diyabet modeli olusturulabilmektedir. Bu derlemede, diyabetik hayvan modelleri ve onemi hakkinda son gelismeler isiginda bilgiler verilmistir.