Caner Cetinkaya

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.

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.

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.

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.

Acute Supramaximal Exercise Increases the Brain Oxygenation in Relation to Cognitive Workload

Single bout of exercise can improve the performance on cognitive tasks. However, cognitive responses may be controversial due to different type, intensity, and duration of exercise. In addition, the mechanism of the effect of acute exercise on brain is still unclear. This study was aimed to investigate the effects of supramaximal exercise on cognitive tasks by means of brain oxygenation monitoring. The brain oxygenation of Prefrontal cortex (PFC) was measured on 35 healthy male volunteers via functional near infrared spectroscopy (fNIRS) system. Subjects performed 2-Back test before and after the supramaximal exercise wingate anerobic test (WAnT) lasting 30-s on cycle ergometer. The PFC oxygenation change evaluation revealed that PFC oxygenation rise during post-exercise 2-Back task was considerably higher than those in pre-exercise 2-Back task. In order to describe the relationship between oxygenation change and exercise performance, subjects were divided into two groups as high performers (HP) and low performers (LP) according to their peak power values (PP) obtained from the supramaximal test. The oxy-hemoglobin (oxy-Hb) values were compared between pre- and post-exercise conditions within subjects and also between subjects according to peak power. When performers were compared, in the HP group, the oxy-Hb values in post-exercise 2-Back test were significantly higher than those in pre-exercise 2-Back test. HP had significantly higher post-exercise oxy-Hb change (Δ) than those of LP. In addition, PP of the total group were significantly correlated with Δoxy-Hb.The key findings of the present study revealed that acute supramaximal exercise has an impact on the brain oxygenation during a cognitive task. Also, the higher the anerobic PP describes the larger the oxy-Hb response in post-exercise cognitive task. The current study also demonstrated a significant correlation between peak power (exercise load) and post-exercise hemodynamic responses (oxy-, deoxy- and total-Hb). The magnitude of this impact might be related with the physical performance capacities of the individuals. This can become a valuable parameter for future studies on human factor.

The effects of resveratrol on chronic constriction injury of sciatic nerve in rats

The aim of this study was to investigate the effects of resveratrol (RVT) in chronic constriction injury (CCI) of sciatic nerve by behavioral, histomorphological and immunohistochemical evaluations in rats. In this study, male Wistar rats were divided into three groups: sham (n=7), CCI+saline (n=7) and CCI+RVT (n=7). After inducing CCI, treatment with 10mg/kg/day of RVT or saline for 14 days was given. Locomotor function was assessed with rota-rod and open field tests. Morphologic alterations of sciatic nerve were assessed histologically by light and electron microscopy. Immunohistochemistry for insulin-like growth factor-1 (IGF-1) were performed. RVT treatment prevented motor impairment and histomorphological alterations caused by chronic constriction injury of sciatic nerve. IGF-1 immunoreactivity was significantly higher in RVT treated group then CCI induced group and positive correlated with morphometric parameters. These results indicate that RVT may reduce CCI induced damage and this effect may be mediated through the restoration of IGF-1 immunoreactivity.

The role of serotonin and serotonin 2A receptor in the anxiety due to traumatic brain injury in immature rats

Objective: The aim of this study is to investigate the relationship between anxiety due to traumatic brain injury (TBI) and prefrontal cortex serotonin (5-HT) and 5-HT2A receptor in immature rats. Methods: Seven days old rats were subjected to traumatic brain injury model. They were divided into five groups. 1-Sham; 2-TBI group; 3-TBI followed by 14 days of administration of essitalopram (selective serotonin reuptake inhibitors; SSRI) (10 mg/kg) group (TBI+SSRI); 4-TBI and cyproheptadine (nonspecific serotonin receptor antagonist; A) (5 mg/kg) given by gastric gavage one hour prior to behavioral tests (TBI+A); 5-TBI followed by 14 days of essitalopram (SSRI) and cyproheptadine (A) given 1 hour prior to behavioral tests (TBI+SSRI+A). Elevated T-maze test and open field test applied to all groups and then blood corticosterone, prefrontal cortex tissue 5-HT and 5-HT2A receptor quantities measured. Prefrontal cortex neuron density histologically evaluated. Results: In the TBI group, the time spent in the peripheral cells, the time spent in the elevated T-maze closed arms, and serum corticosterone levels found to increase as a result of anxiety. Neuronal density decreased in prefrontal cortex. SSRI treatment reduced the time spent on the closed arms in the elevated T-maze test. SSRI decreased serum corticosterone levels and increased neuronal density. Tissue serotonin levels decreased in all groups exposure to TBI compared to sham group. 5-HT2A receptor levels were higher in the TBI and A group. Conclusion: SSRIs showed anxiolytic effect for anxiety, secondary to TBI in immature rats.