Ali Riza Sisman

Effects of voluntary and involuntary exercise on cognitive functions, and VEGF and BDNF levels in adolescent rats

Abstract Regular treadmill running during adolescence improves learning and memory in rats. During adolescence, the baseline level of stress is thought to be greater than during other periods of life. We investigated the effects of voluntary and involuntary exercise on the prefrontal cortex and hippocampus, vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF) levels, and spatial learning, memory and anxiety in adolescent male and female rats. The voluntary exercise group was given free access to a running wheel for 6 weeks. The involuntary exercise group was forced to run on a treadmill for 30 min at 8 m/min 5 days/week for 6 weeks. Improved learning was demonstrated in both exercise groups compared to controls. Neuron density in the CA1 region of the hippocampus, dentate gyrus and prefrontal cortex were increased. Hippocampal VEGF and BDNF levels were increased in both exercise groups compared to controls. In females, anxiety and corticosterone levels were decreased; BDNF and VEGF levels were higher in the voluntary exercise group than in the involuntary exercise group. The adolescent hippocampus is affected favorably by regular exercise. Although no difference was found in anxiety levels as a result of involuntary exercise in males, females showed increased anxiety levels, and decreased VEGF and BDNF levels in the prefrontal cortex after involuntary exercise.

The Levels of Soluble CD40 Ligand and C-Reactive Protein in Normal Weight, Overweight and Obese People

Objective: Obesity has been suggested as an independent risk factor for cardiovascular disease. Increasing evidence shows that engagement of soluble CD40 ligand (sCD40L) with its receptor plays a crucial role in the pathogenesis of atherosclerosis. The aim of the present study was to test whether obesity is associated with low-grade systemic inflammation as measured by serum high-sensitive C-reactive protein (hsCRP) and sCD40L concentration. Methods: Serum hsCRP and sCD40L concentrations were measured in 148 nondiabetic people. The participants were divided into three groups depending upon their body mass index (BMI) levels: Group 1 (normal weight), BMI<25 kg/m2; Group 2 (overweight), BMI 25 kg/m2 to 29.9 kg/m2; and Group 3 (obese), BMI≥30 kg/m2. Results: Obese people had more elevated hsCRP levels than both their normal weight and overweight counterparts (P=0.000 and P=0.000, respectively). Similarly, serum concentrations of sCD40L were significantly higher, statistically, in obese subjects compared with normal weight subjects (P=0.003). In addition, obese subjects had higher values of sCD40L than overweight subjects, but the difference did not reach statistical significance (P=0.063). The levels of high-density lipoprotein cholesterol were significantly lower in obese subjects compared to normal weight subjects (P=0.048). The analysis of platelet count disclosed a statistically significant difference between obese subjects and normal weight subjects (P=0.028). The levels of BMI were positively correlated with the serum levels of hsCRP and sCD40L in all subjects (r=0.514, P=0.000 and r=0.283, P=0.000, respectively). Levels of hsCRP were positively correlated with waist circumference, fasting glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, leukocytes, platelets, systolic and diastolic blood pressure. Similarly, soluble CD40L levels were positively correlated with waist circumference, fasting glucose and leukocytes. Conclusion: Obese patients showed a significant increase of hsCRP and sCD40L levels compared with normal weight subjects, which might contribute to the known proinflammatory milieu found in these patients.

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.

Anxiety correlates to decreased blood and prefrontal cortex IGF-1 levels in streptozotocin induced diabetes

It is well known that diabetes mellitus may cause neuropsychiatric disorders such as anxiety disorders. Diabetes may also cause reduced IGF-1 (insulin like growth factor-1) levels in brain and blood. The purpose of the present study was to investigate the relationship between diabetes induced anxiety and IGF-1 levels in diabetic rats. The anxiety levels of rats were assessed 2 weeks after intraperitoneal injection of streptozotocin. Diabetic rats had higher levels of anxiety, as they spent more time in closed branches in elevated-plus-maze-test and less time in the center cells of open-field-arena. Prefrontal cortex (PFC) IGF-1 levels and neuron numbers were decreased and apoptosis was increased in diabetic rats. Blood IGF-1 levels decreased in a time dependent fashion following streptozotocin injection while blood corticosterone levels increased. They had higher malondialdehyde levels and lower superoxide dismutase enzyme activity. Oxidative stress may negatively affect blood and PFC tissue IGF-1 levels. Reduction in IGF-1 may cause PFC damage, which may eventually trigger anxiety in diabetic rats. Therapeutic strategies that increase blood and brain tissue IGF-1 levels may be promising to prevent psychiatric sequelae of diabetes mellitus.

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.

Enhanced levels of soluble CD40 ligand and C-reactive protein in a total of 312 patients with metabolic syndrome

The metabolic syndrome (MS) is associated with a systemic inflammatory response that plays an important pathogenetic role in atherothrombotic disease. Increasing evidence indicates that CD40-CD40 ligand interactions constitute an important mediator for vascular inflammation. The purpose of this study was to assess whether high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) levels were increased in patients with MS. During the study period from January 2004 to August 2004, 312 patients with MS and 98 control subjects were included. Anthropometric measurements, blood pressure assessment, electrocardiography, and blood measurements including fasting blood glucose, postprandial blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, glycated hemoglobin, white blood cell (WBC), platelets, hs-CRP, and sCD40L were performed. Patients with MS were divided into 3 groups based upon their glucose tolerance (group 1, normal glucose tolerance; group 2, prediabetic group; and group 3, diabetes mellitus). Patients with MS showed a significant increase of WBC, hs-CRP, and sCD40L levels compared with control subjects. The levels of both hs-CRP and sCD40L were positively correlated with body mass index (BMI). High-sensitivity CRP levels were also positively correlated with waist circumferences, fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, and negatively correlated with high-density lipoprotein cholesterol. In patients with MS, both hs-CRP and sCD40L levels were positively correlated with WBC count. We found a positive correlation between sCD40L and platelets. Among the subgroups of patients with MS, the mean levels of WBC, hs-CRP, and sCD40L did not show any significant differences. In conclusion, elevated levels of WBC, hs-CRP, and sCD40L in MS patients provide further insight into the relationship between MS and inflammation. In our study, positive correlations between BMI and both hs-CRP and sCD40L levels suggest that BMI is an important determinant of a chronic inflammatory state in patients with MS. Moreover, this study reports significantly increased levels of WBC, hs-CRP, and sCD40L not only in diabetic subjects with MS but also in prediabetic subjects and nondiabetic subjects with MS compared with control subjects. Our data suggest that MS patients have proinflammatory state independent of their glucose tolerance status. In our study, the positive correlation between the levels of sCD40L and platelets in patients with MS supports previous reports indicating that sCD40L are derived predominantly from platelets.

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.

Positive effects of aerobic exercise on learning and memory functioning, which correlate with hippocampal IGF-1 increase in adolescent rats.

It is already known that regular aerobic exercise during adolescent period improves learning and memory in rats. In this study, we investigated the effects of regular aerobic exercise on learning, memory functioning and IGF-1 levels. IGF-1 is known to have positive effects on cognitive functions in adolescent rats. Exercise group was separated into two different groups. First half was run on a treadmill for 30 min per session at a speed of 8m/min and 0° slope, five times a week for 6 weeks. The second half was given free access to a running wheel (diameter 11.5 cm) which was connected to a digital counter and run on a treadmill for 6 weeks. Learning and memory functioning were found to be positively correlated with the exercise activity. Findings suggest increased neuron density in CA1 hippocampal region and dentate gyrus. Increased IGF-1 level was detected in hippocampus and blood serum, while IGF-1 level in liver tissue did not change with exercise activity. In conclusion, our findings indicate that learning and memory functioning were positively affected by voluntary and involuntary physical exercise which correlated increased hippocampal activity and elevated IGF-1 levels in adolescent rats.

Potential novel biomarkers for diabetic testicular damage in streptozotocin-induced diabetic rats: nerve growth factor Beta and vascular endothelial growth factor.

Background. It is well known that diabetes mellitus may cause testicular damage. Vascular endothelial growth factor (VEGF) and nerve growth factor beta (NGF-β) are important neurotrophic factors for male reproductive system. Objective. We aimed to investigate the correlation between testicular damage and testicular VEGF and NGF-β levels in diabetic rats. Methods. Diabetes was induced by streptozotocin (STZ, 45 mg/kg/i.p.) in adult rats. Five weeks later testicular tissue was removed; testicular VEGF and NGF-β levels were measured by ELISA. Testicular damage was detected by using hematoxylin and eosin staining and periodic acid-Schiff staining, and apoptosis was identified by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL). Seminiferous tubular sperm formation was evaluated using Johnsens score. Results. In diabetic rats, seminiferous tubule diameter was found to be decreased; basement membrane was found to be thickened in seminiferous tubules and degenerated germ cells. Additionally, TUNEL-positive cells were increased in number of VEGF+ cells and levels of VEGF and NGF-β were decreased in diabetic testes. Correlation between VEGF and NGF-β levels was strong. Conclusion. These results suggest that the decrease of VEGF and NGF-β levels is associated with the increase of the apoptosis and testicular damage in diabetic rats. Testis VEGF and NGF-β levels could be potential novel biomarkers for diabetes induced testicular damage.