Ayfer Dayi

Relationship between circulating IGF-1 levels and traumatic brain injury-induced hippocampal damage and cognitive dysfunction in immature rats.

It is well known that traumatic brain injury (TBI) induces the cognitive dysfunction resulting from hippocampal damage. In the present study, we aimed to assess whether the circulating IGF-I levels are associated with cognition and hippocampal damage in 7-day-old rat pups subjected to contusion injury. Hippocampal damage was examined by cresyl violet staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Spatial memory performance was assessed in the Morris water maze. Serum IGF-1 levels decreased in both early and late period of TBI. Decreased levels of serum IGF-1 were correlated with hippocampal neuron loss and spatial memory deficits. Circulating IGF-1 levels may be predictive of cognitive dysfunction resulted from hippocampal damage following traumatic injury in developing brain. Therapy strategies that increase circulating IGF-1 may be highly promising for preventing the unfavorable outcomes of traumatic damage in young children.

Maternal treadmill exercise during pregnancy decreases anxiety and increases prefrontal cortex VEGF and BDNF levels of rat pups in early and late periods of life

In a previous study we demonstrated that, regular aerobic exercise during pregnancy decreased maternal deprivation induced anxiety. The purpose of this study is to investigate whether the positive effects of maternal exercise on the male and female offsprings early and late period of life. Half of the test subjects in each group were evaluated when they were 26 days old, and the other half were evaluated when they were 4 months old. The anxiety levels of maternally exercised groups were less than the control groups in both sexes and in both prepubertal and adult periods. The locomotor activity more increased in females. The prefrontal VEGF and BDNF levels were greater for both age groups and sexes in the maternally exercised group compared to control group. Moreover, there was a strong positive correlations between prefrontal cortex BDNF levels and results of open field tests; and VEGF levels and results of elevated plus maze tests. There was no difference in serum corticosterone levels between groups. These results indicate that maternal exercise during pregnancy may protect the pups from anxiety in early and late periods of life, and affects the prefrontal cortex positively.

Maternal exercise decreases maternal deprivation induced anxiety of pups and correlates to increased prefrontal cortex BDNF and VEGF

Maternal deprivation (MD) may cause neuropsychiatric disorders such as anxiety disorder by negatively affecting the cognitive functions and behavior in pups. The aim of this study is to investigate whether maternal exercise during pregnancy has beneficial effects on anxiety that increases with MD, and on the levels of VEGF and BDNF which have anxiolytic effects on the prefrontal cortex, the anxiety-related region of the brain. The anxiety level in the deprivation group was greater than the control group and found more in male than female pups. The prefrontal cortex VEGF and BDNF levels were decreased in the deprivation group compared to control group while serum corticosterone levels were increased in the deprivation group. Anxiety and serum corticosterone levels were decreased in maternally exercised female and male pups, while the prefrontal cortex VEGF and BDNF levels were increased, compared to sedentary mothers pups. These results indicate that maternal exercise may attenuate the negative effect of stresses such as maternal deprivation that can be encountered early in life.

The effects of single dose of methamphetamine on lipid peroxidation levels in the rat striatum and prefrontal cortex

The administration of methamphetamine to experimental animals results in damage to dopaminergic neurons. In the present study, we demonstrated that a single dose (15 mg/kg) of methamphetamine results in production of oxidative stress as demonstrated by increased thiobarbituric acid reactive substances levels in the rat striatum and prefrontal cortex. In conclusion, the results of present study provide further evidence in support of the notion that oxidative stress may play an important role in the methamphetamine-induced neurotoxicity.

Acute footshock-stress increases spatial learning–memory and correlates to increased hippocampal BDNF and VEGF and cell numbers in adolescent male and female rats

It is well known that the acute-stress enhances cognitive functions in adults, but is not known in adolescents. The purpose of this study is to investigate the effects of low and high intensities of acute-stress on hippocampus and spatial memory in the adolescent male and female rats. Thirty-eight days aged rats were subjected to 0.2 and 1.6 mA intensity of footshock-stress for 20 min. Spatial memory performance was assessed in the Morris water maze. Learning had been positively affected in stress groups. Neuron density in the CA1 hippocampal region and the gyrus dentatus as well as VEGF and BDNF levels of hippocampus increased in all stress groups. In females, learning process and BDNF levels increased in low-intensity-stress group than high-intensity-stress group. There was no difference in hippocampal apoptosis among groups. We conclude that adolescent hippocampus is affected positively from acute-stress; however, while there is no difference in male response with respect to intensity of stress, females are affected more positively from low-intensity of stress.

Combined treatment with progesterone and magnesium sulfate positively affects traumatic brain injury in immature rats.

AIM It is well known that head trauma results in damage in hippocampal and cortical areas of the brain and impairs cognitive functions. The aim of this study is to explore the neuroprotective effect of combination therapy with magnesium sulphate (MgSO4) and progesterone in the 7-days-old rat pups subjected to contusion injury. MATERIAL AND METHODS Progesterone (8 mg/kg) and MgSO4 (150 mg/kg) were injected intraperitoneally immediately after induction of traumatic brain injury. Half of groups were evaluated 24 hours later, the remaining animals 3 weeks after trauma or sham surgery. Anxiety levels were assessed with open field activity and elevated plus maze; learning and memory performance were evaluated with Morris Water maze in postnatal 27 days. RESULTS Combined therapy with progesterone and magnesium sulfate significantly attenuated trauma-induced neuronal death, increased brain VEGF levels and improved spatial memory deficits that appear later in life. Brain VEGF levels were higher in rats that received combined therapy compared to rats that received either medication alone. Moreover, rats that received combined therapy had reduced hipocampus and prefrontal cortex apoptosis in the acute period. CONCLUSION These results demonstrate that combination of drugs with different mechanisms of action may be preferred in the treatment of head trauma.

Age-related changes in apoptosis in rat hippocampus induced by oxidative stress

Also known as programmed cell death, apoptosis is a sequence of events that leads to elimination of cells without releasing harmful substances into the surrounding area. Apoptosis may be induced by intracellular or extracellular signals. Certain apoptotic signals activate mitochondrial pro-apoptotic events and increase reactive oxygen species (ROS). Increased ROS production may lead to oxidative stress. The goal of our study was to characterize age-related changes in apoptosis induced by oxidative stress in the hippocampus. Rats 2, 7, 21 and 38 days old, and adult rats were used for our study. Hippocampal CA1, CA2, CA3 and dentate gyrus apoptosis, and hippocampal superoxide dismutase (SOD), glutathione peroxidase (GPx) enzyme activities and thiobarbituric acid reactive substances (TBARS) levels were measured. We found that numbers of hippocampal neurons were low in rats 2, 7 and 21 days old (CA1, p < 0.001; CA3, p < 0.05; gyrus dentatus, p < 0.001). The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cell count was highest in the CA1 and dentate gyrus of 21-day-old rats. Among 21-day-old rats, the hippocampal TBARS levels and SOD enzyme activity were high, whereas GPx activity was low. These results demonstrate that the hippocampal CA1 and dentate gyrus of 21-day-old rats are more prone to damage by oxidative stress.

Progesterone treatment decreases traumatic brain injury induced anxiety and is correlated with increased serum IGF-1 levels; prefrontal cortex, amygdala, hippocampus neuron density; and reduced serum corticosterone levels in immature rats

Abstract Traumatic brain injury (TBI) may cause neuropsychiatric problems, such as anxiety disorder, that have negative effects on cognitive functions and behavior. We investigated the effects of progesterone on traumatic brain injury induced anxiety in 7-day-old rat pups subjected to contusion injury. Progesterone treatment decreased TBI induced anxiety and serum corticosterone levels, and increased serum IGF-1 levels. Moreover, progesterone treatment increased amygdala, prefrontal cortex and hippocampal neuron density. We found a negative correlation between serum corticosterone levels and anxiety tests, and a positive correlation between serum IGF-1 levels and anxiety tests. In addition, progesterone treatment decreased serum corticosterone compared to the controls and sham. Our results indicate that single dose progesterone may be effective for treating anxiety caused by TBI.

The Effects of Oxytocin on Cognitive Defect Caused by Chronic Restraint Stress Applied to Adolescent Rats and on Hippocampal VEGF and BDNF Levels

Background Because brain development continues during adolescence, the effects of chronic stress on hippocampal changes that occur during that period are permanent. Oxytocin, which is synthesized in the hypothalamus and has many receptors in brain regions, including the hippocampus, may affect learning-memory. This study aimed to investigate chronic restraint stress on hippocampal functions, and hippocampal vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) levels in adolescent male and female rats and the role of oxytocin in these effects. Material/Methods Experimental groups included control, stress+oxytocin, and stress+saline groups. Restraint stress was applied to all the stress groups for 1 h/day, for 7 days. Learning-memory tests were performed after the 7th day. Results In the stress+oxytocin groups, the process of finding the platform was shorter than in others groups. The stress+saline groups spent less time, whereas the stress+oxytocin groups spent more time, on the target quadrant in the probe trial. In the stress+oxytocin groups thigmotaxis time (indicating anxiety) decreased, but VEGF and BDNF levels increased. A positive correlation was found between VEGF and BDNF levels and the time spent within the target quadrant. Conclusions The results indicate that impaired hippocampal learning and memory loss due to chronic restraint stress can be positively affected by intranasal oxytocin.

Anxiety- and depression-like behavior are correlated with leptin and leptin receptor expression in prefrontal cortex of streptozotocin-induced diabetic rats.

Abstract Anxiety and depression are common in diabetics. Diabetes also may cause reduced leptin levels in the blood. We investigated the relation between diabetes induced anxiety- and depression-like behavior, and leptin and leptin receptor expression levels in diabetic rats. The anxiety- and depression-like behaviors of rats were assessed 4 weeks after intraperitoneal injection of streptozotocin. Diabetic rats exhibited greater anxiety-like behavior; they spent more time in closed branches of the elevated plus maze test and less time in the center cells of the open field arena. Increased depression-like behavior was observed in diabetic rats using the Porsolt swim test. Prefrontal cortex (PFC), blood leptin levels and PFC neuron numbers were decreased, and leptin receptor expression and apoptosis were increased in diabetic rats. Blood corticosterone levels also were increased in diabetic rats. These results indicate that reduction of leptin up-regulates leptin receptor expression and may affect PFC neurons, which eventually triggers anxiety- and depression-like behaviors in diabetic rats.