The Effects of Prenatal and Postnatal Exposure to 50-Hz and 3 mT Electromagnetic Field on Rat Testicular Development.

Background and objectives: It has been shown that electromagnetic fields (EMFs) have negative effects on the reproductive system. The biological effects of EMF on the male reproductive system are controversial and vary depending on the frequency and exposure time. Although a limited number of studies have focused on the structural and functional effects of EMF, the effects of prenatal and postnatal EMF exposure on testes are not clear. We aimed to investigate the effects of 50-Hz, 3-mT EMF exposure (5 days/wk, 4 h/day) during pre- and postnatal periods on testis development. Materials and Methods: Pups from three groups of Sprague-Dawley pregnant rats were used: Sham, EMF-28 (EMF-exposure applied during pregnancy and until postnatal day 28), EMF-42 (EMF-exposure applied during pregnancy and until postnatal day 42). The testis tissues and blood samples of male offspring were collected on the postnatal day 42. Results: Morphometric analyses showed a decrease in seminiferous tubule diameter as a result of testicular degeneration in the EMF-42 group. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were decreased in the EMF-42 group. Lipid peroxidation levels were increased in both EMF groups, while antioxidant levels were decreased only in the EMF-28 group. We found decreased levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF1) in the EMF-42 group, and decreased levels of the SRC homology 3 (SH3) and multiple ankyrin repeat domain (SHANK3) in the EMF-28 group in the testis tissue. Conclusions: EMF exposure during pre- and postnatal periods may cause deterioration in the structure and function of testis and decrease in growing factors that would affect testicular functions in male rat pups. In addition to the oxidative stress observed in testis, decreased SHANK3, VEGF, and IGF1 protein levels suggests that these proteins may be mediators in testis affected by EMF exposure. This study shows that EMF exposure during embryonic development and adolescence can cause apoptosis and structural changes in the testis.

Erythropoietin diminishes isoflurane-induced apoptosis in rat frontal cortex.

BACKGROUND: During the brain growth spurt, anesthetic drugs can cause cellular and behavioral changes in the developing brain. The aim of this study was to determine the neuroprotective effect of erythropoietin after isoflurane anesthesia in rat pups. METHODS: A total of 42, 7-day-old Wistar rats were divided into three groups. Control group (GC; n = 14): Rats breathed 100% oxygen for 6 h; Isoflurane group (GI; n = 14): Rats were exposed to 1.5% isoflurane in 100% oxygen for 6 h; Isoflurane + erythropoietin group (GIE; n = 14): 1000 IU·kg(-1) (intraperitoneal; IP) Erythropoietin was administered after isoflurane anesthesia. Each group was divided into two groups for pathology and learning and memory tests. Silver, caspase-3, and fluoro-jade C staining were used for detecting apoptotic cells in frontal cortex, striatum, hippocampus, thalamus, and amygdala. Morris water maze was used to evaluate learning and memory. RESULTS: There was a significant increase in apoptotic cell count after isoflurane anesthesia in the frontal cortex when compared with control group (29.0 ± 9.27 vs 3.28 ± 0.75 [P = 0.002], 20.85 ± 10.94 vs 2.0 ± 0.81 [P = 0.002] and 24.57 ± 10.4 vs 5.14 ± 0.69 [P = 0.024] with silver, caspase-3, and fluoro-jade C staining, respectively). The apoptotic cell count in the frontal cortex was significantly higher in GIE than GC with caspase-3 staining (9.14 ± 3.13 vs 2.0 ± 0.81, P = 0.002). The apoptotic cell count in GIE was significantly reduced in the frontal cortex when compared with GI (4.0 ± 0.81 vs 29.0 ± 9.27 [P = 0.002], 9.14 ± 3.13 vs 20.85 ± 10.94 [P = 0.04] and 4.0 ± 1.63 vs 24.57 ± 10.4 [P = 0.012] with silver, caspase-3, and fluoro-jade C staining, respectively). CONCLUSIONS: A total of 1000 IU·kg(-1) IP erythropoietin diminished isoflurane-induced neuroapoptosis. Further experimental studies have to be planned to reveal the optimal dose and timing of erythropoietin before adaptation to clinical practice.

Effects of administration of subtoxic doses of acetaminophen on liver and blood levels of insulin-like growth factor-1 in rats.

Acetaminophen (APAP) is widely used in the treatment of pain. Toxic doses of APAP cause acute liver failure, but therapeutic doses are believed to be safe. The purpose of this study is to investigate the effects of administration of subtoxic doses of APAP on liver and blood levels of insulin-like growth factor-1 (IGF-1) in rats. Low dose (100 mg/kg) and high dose (250 mg/kg) of APAP were intraperitoneally injected into Wistar albino rats. Following administration of therapeutic doses of APAP, there were no significant changes in serum transaminases and liver glutathione levels. Both doses of APAP induced a decrease in liver and blood levels of IGF-1 when compared with the controls. There was no significant difference in liver IGF-1 levels between the high-dose and low-dose APAP groups; however, there was a significant difference in blood IGF-1 levels between both the groups. The histological examination showed that low dose of APAP induced mild degree of structural change, while high dose of APAP induced severe structural damage. In conclusion, these results suggest that blood IGF-1 levels may have a value in predicting hepatic damage resulting from therapeutic doses of APAP.

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.

The effects of Spirulina platensis on behavior in adolescent rats fed a high-fat diet.

In recent years, childhood overweight and obesity have become a universal public health problem. Obesity may lead to cognitive disorders, depression and anxiety by affecting neuronal processes. Spirulina platensis (SP), a species of microalgae from the Chlorophyceae green algae class, has neuroprotective effects and may reduce body weight. In this study, we aimed to investigate the effects of SP on behavior alongside the role of leptin and Sirtuin-1 in fed with high-fat diet (HFD) adolescent rats. Four-week-old Sprague Dawley male rats were divided into four groups: control, HFD, HFD + SP150 (150 mg/kg/day SP, orally), HFD + SP450 (450 mg/kg/day SP, orally). Rats except for the control group exposed to 60% HFD along 12 weeks. Last 6 weeks SP or vehicle administered. After the behavioral tests, leptin and Sirtuin-1 levels in prefrontal cortex and hippocampus regions were evaluated. SP150 significantly reduced body weight compared with HFD group. The time spent in the center of open field increased significantly in SP150-treated rats compared with HFD. SP150 and SP450 significantly decreased immobility time in forced swim test compared with HFD. Leptin levels in HFD group were significantly lower in prefrontal cortex compared to control group. Leptin levels of the HFD + SP450 group were significantly higher than HFD group in the hippocampus. There was no significant difference between groups in Sirtuin-1 levels. In conclusion, SP supplementation in adolescence period might positively affect chronic high fat-induced anxiety-like and depressive-like behavior by partially affecting brain leptin levels and without affecting Sirtuin-1 levels.

The effects of bee venom on behavior and the role of leptin in rats.

The aim of this study is to evaluate the dose­dependent effect of bee venom (BV) on behavioral functions in rats and the physiological role of leptin in the prefrontal cortex, hippocampus, and amygdala tissues. Adult Sprague­Dawley male rats were used in the experiments. The rats were divided into three groups of control, 0.1 mg/kg BV, and 0.5 mg/kg BV. The rats were injected with BV subcutaneously for 15 consecutive days. The open field test (OFT), the elevated plus maze test (EPM), and the forced swimming test (FST) were performed as behavioral assessments. Animals were sacrificed, and brain regions were removed. Leptin levels were measured in various brain regions by ELISA. In the OFT, the total distance and speed for the 0.1 mg/kg BV group increased compared to controls and the 0.5 mg/kg BV group. In the EPM, the 0.1 mg/kg BV group remained in the open arm for a significantly longer period of time compared to the other groups. In the FST, the 0.5 mg/kg BV group was more mobile than the other groups. Leptin levels in the prefrontal cortex were significantly higher in the 0.1 mg/kg BV group compared to the control and 0.5 mg/kg groups. There were no significant differences between groups in hippocampus and amygdala leptin levels. The results of the study show that BV has a positive effect on behavioral parameters. BV may have a positive effect on anxiety­ and depression­like behaviors by increasing leptin levels in the prefrontal cortex.

Maternal aerobic exercise during pregnancy can increase spatial learning by affecting leptin expression on offspring's early and late period in life depending on gender.

Maternal exercise during pregnancy has been suggested to exert beneficial effects on brain functions of the offspring. Leptin is an adipocytokine which is secreted from adipose tissues and has positive effects on learning, memory, and synaptic plasticity. In this study, pregnant rats were moderately exercised and we observed the effects of this aerobic exercise on their prepubertal and adult offsprings' spatial learning, hippocampal neurogenesis, and expression of leptin. All the pups whose mothers exercised during pregnancy learned the platform earlier and spent longer time in the target quadrant. Their thigmotaxis times were shorter than those measured in the control group. It is shown that hippocampal CA1, CA3 neuron numbers increased in both prepubertal and adult pups, in addition that GD neuron numbers increased in adult pups. Leptin receptor expression significantly increased in the prepubertal male, adult male, and adult female pups. In our study, maternal running during pregnancy resulted in significant increase in the expression of leptin receptor but not in prepubertal female pups, enhanced hippocampal cell survival, and improved learning memory capability in prepubertal and adult rat pups, as compared to the control group. In conclusion, maternal exercise during pregnancy may regulate spatial plasticity in the hippocampus of the offspring by increasing the expression of leptin.

Gender differences in effects of prenatal and postnatal exposure to electromagnetic field and prenatal zinc on behaviour and synaptic proteins in rats.

Humans are exposed to electromagnetic fields (EMF) from various sources throughout life. Because humans are easily impacted by environmental factors during early development, it is believed that EMF can cause structural and functional changes on the developing brain that may lead to behavioural changes. This paper investigates the impact of EMF exposure and zinc supplementation during the prenatal and postnatal periods on behavioural changes and synaptic proteins in a gender-dependent manner. Pups from four groups of pregnant rats were used: Sham, EMF (5 days/wk, 4 h/day EMF-exposure applied), Sham+Zinc (5 days/wk, 5 mg/kg/day zinc applied) and EMF+Zinc (5 days/wk, 4 h/day EMF-exposure and 5 mg/kg/day zinc applied). EMF exposure and zinc supplementation were initiated from the first day of pregnancy to the 42nd postnatal day. Zinc levels in blood, NLGN3 and SHANK3 levels in hippocampus and amygdala, and synaptic structures in amygdala were examined. Behavioural tests showed that EMF exposure had no effect on social behaviour, but adversely affected activity and exploratory behaviour, and led to increased anxiety formation. Zinc supplementation had a partially positive effect on female, but not male offspring. SHANK3 and NLGN3 proteins were significantly lower in EMF groups, however, no positive effect of zinc supplementation was found. In conclusion, EMF exposure may alter the levels of synaptic proteins in the developing brain, leading to behavioural changes in a gender-dependent manner. Evaluation of zinc supplementation at different doses could be beneficial to prevent or reduce the behavioural and structural effects of EMF.

The effects of bee venom on liver and skeletal muscle in exhaustive swimming rats.

Oxidative damage and proinflammatory cytokines are involved in exhaustive exercise-induced fatigue. This study aimed to investigate the effects of bee venom, a natural toxin, on fatigue and tissue damage in rats that underwent forced swimming exercise. Rats were divided into four groups: control, swimming exercise (SE), bee venom (BV) and swimming exercise + bee venom (SE + BV). SE and SE + BV groups were subjected to forced swimming (load of 7% body weight) for 5 days. BV and SE + BV groups were injected with 1 mg/kg BV subcutaneously. Swimming time, blood lactate and TNF-α levels, MDA and GSH levels in liver and gastrocnemius muscle were evaluated. Swimming time was shorter in SE + BV group than SE group. There was no difference in lactate levels between SE and SE + BV groups. MDA and GSH levels were increased in SE, BV and SE + BV groups. TNF-α levels were increased in BV group compared to control and SE groups. Our study demonstrated that BV administration before exhaustive exercise in rats did not provide anti-fatigue effect. Additionally, BV did not show anti-inflammatory activity and had different effects on antioxidant capacity at tissue level. Further research might explore the effects of different doses and durations of BV on exhaustive exercise.

A Comparison of the Effectiveness of Silibinin and Resveratrol in Preventing Alpha-Amanitin-Induced Hepatotoxicity.

Amanita phalloides species mushrooms containing alpha-amanitin (α-AMA) are responsible for the majority of fatal mushroom intoxications and can lead to severe poisonings resulting in hepatotoxicity and acute hepatic failure. Existing antidotes, such as silibinin, are not sufficiently effective in the prevention and/or resolution of α-AMA-induced hepatotoxicity. We investigated the effects of resveratrol on α-AMA-induced hepatotoxicity and compared with silibinin, a known antidote using in vivo and in vitro toxicity models. In the in vivo protocol, resveratrol (30 mg/kg) was given simultaneously with α-AMA (α-AMA + SR) or 12 (α-AMA + 12R) or 24 (α-AMA + 24R) hr after α-AMA administration. Silibinin (5 mg/kg) (α-AMA + Sil) and normal saline (α-AMA + NS) were given simultaneously with α-AMA. We found that liver transaminase levels in α-AMA + SR and α-AMA + 12R groups and histomorphologic injury score in the α-AMA + SR, α-AMA + 12R, α-AMA + 24R and α-AMA + Sil groups were significantly lower than that of the α-AMA + NS group. Resveratrol decreased mononuclear cell infiltration, necrosis and active caspase-3 immunopositivity in the liver. In the in vitro protocol, the effects of resveratrol and silibinin were evaluated in a reduction in cell viability induced by α-AMA in THLE-2 and THLE-3 hepatocytes. Neither resveratrol nor silibinin was found to be effective in increasing cell viability decreased by α-AMA + NS. As a conclusion, resveratrol was found to be effective in α-AMA-induced hepatotoxicity with its anti-inflammatory properties in in vivo conditions. It is a promising compound with the potential for use in the treatment of hepatotoxicity associated with Amanita phalloides type mushroom poisonings.

The effect of melatonin on endotoxemia-induced intestinal apoptosis and oxidative stress in infant rats.

OBJECTIVE: To evaluate the effect of melatonin on the intestinal apoptosis along with oxidative damage in endotoxemic infant rats. DESIGN AND SETTING: Prospective animal study in a university-based experimental research laboratory. SUBJECTS AND INTERVENTIONS: Wistar albino 7-day-old rat pups (n=21). The animals were randomized into three experimental groups: (1) controls; (2) endotoxemia; (3) endotoxemia treated with melatonin (10mg/kg). Endotoxemia was induced in rats by intraperitoneal injection of lipopolysaccharide (Escherichia coli serotype 0111:B4; 3 mg/kg). MEASUREMENTS AND RESULTS: Four hours after LPS injection, the antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and thiobarbituric acid reactive substance (TBARS) levels as an indicator of lipid peroxidation, were determined. Intestinal apoptosis was assessed by hematoxylin-eosin staining and terminal deoxynucleotide transferase-mediated fluorescein-dUTP nick end labeling. The administration of melatonin into endotoxemic rats prevented the increase in the TBARS levels, and increased the activities of antioxidant enzymes and attenuated apoptotic cell death in both intestinal epithelium and lamina propria. CONCLUSIONS: Melatonin diminished the intestinal oxidative stress and apoptotic damage induced by endotoxemia in infant rats.

Suppression of apoptosis and oxidative stress by deprenyl and estradiol in aged rat liver.

Aging is accompanied by significant structural and functional transformations of all organs and systems. Age-associated increase in apoptotic behavior may cause disease. Older cells are more susceptible to endogenous oxidative damage, and oxidative stress is a potent inducer of apoptosis. Deprenyl is an irreversible monoamine-oxidase B inhibitor which has anti-oxidant, anti-apoptotic and neuroprotective effects. Estrogen is also a neuroprotective and anti-oxidant hormone. The objectives of this study were to determine whether the anti-oxidative effects of deprenyl can suppress apoptotic activity, with or without estradiol, in aged female rat livers. In this study, ovariectomized female Wistar albino rats were divided into six groups as follows; young (3 months old) saline-treated control, aged (24 months old) saline-treated control, aged deprenyl treated, aged estradiol treated, aged deprenyl plus estradiol treated and aged sham controls. All rats except for the sham group were treated for 21 days. Determination of oxidative stress parameters was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining was performed. The results were analyzed by one-way ANOVA post hoc Bonferroni test. Deprenyl and estradiol administration, alone or in combination, decreased significantly the levels of lipid peroxidation and increased superoxide dismutase activity in the liver relative to aged control and sham rats (P<0.05). The number of TUNEL positive cells decreased significantly in deprenyl and estradiol-treated rats compared with aged control and sham rats. The results indicate that deprenyl treatment alone, or in combination with estradiol, may modulate age-related apoptotic changes in rat liver by decreasing oxidative stress.

Exercise increases leptin levels correlated with IGF-1 in hippocampus and prefrontal cortex of adolescent male and female rats.

It is known that regular aerobic exercise has positive effects on hippocampus and prefrontal cortex. We have previously have been able to demonstrate that aerobic exercise increased IGF-1 in hippocampus. Leptin, which is associated with cognitive functions, is also involved in fat metabolism and stimulates energy consumption. While it is known that leptin stimulates IGF-1 production in hepatocytes, little known is on the link between IGF-1 and leptin in brain during aerobic exercise. In this study, we investigated the effects of regular aerobic exercise on leptin, leptin receptor expression levels in hippocampus and prefrontal cortex. Additionally, we investigated the correlation of IGF-1 levels with leptin and leptin receptor expression. During the experiment, exercise group was run on a treadmill for 30min per session at a speed of 8m/min and 0° slope, five times a week for 6 weeks. Leptin, leptin expression, IGF-1 levels and cell numbers increased in prefrontal cortex and hippocampus of exercise groups. Blood leptin levels increased in female rats in exercise group; whereas it did not change in male rats; blood IGF-1 levels were found to be increased in exercised male rats. There was a strong positive correlation between hippocampal leptin levels and hippocampal IGF-1 levels; also a strong positive correlation between hippocampal leptin receptor expression and hippocampal IGF-1. These results indicate that, increased leptin and leptin receptor expression are correlated with IGF-1 in regular aerobic exercised rats. Blood leptin and IGF-1 levels were also found to be associated with gender. Females had high blood leptin levels and males had high blood IGF-1 levels in the exercise groups.

Acute exhaustive exercise does not alter lipid peroxidation levels and antioxidant enzyme activities in rat hippocampus, prefrontal cortex and striatum.

Although regular physical exercise is beneficial to the body, it is well known that exhaustive exercise causes oxidative stress in muscle. Recent studies suggest that regular moderate physical exercise has the beneficial effects on brain. However, there is little information regarding whether or not exhaustive exercise could generate oxidative stress in brain and the findings are conflicting. The aim of this study was to investigate the effects of exhaustive exercise on thiobarbituric acid reactive substances, as an indicator of lipid peroxidation, in the hippocampus, prefrontal cortex and striatum. Additionally we examined antioxidant enzymes activities, superoxide dismutase and glutathione peroxidase, to assess the effects of reactive oxygen species. Exhaustive exercise did not change superoxide dismutase and glutathione peroxidase enzyme activities and thiobarbituric acid reactive substances levels neither immediately (0 min) nor at 3, 6, 12, 24 and 48 h after the cessation of exercise in the brain. These results indicate that acute exhaustive exercise may not cause significant lipid peroxidation in the hippocampus, prefrontal cortex and striatum during the post-exercise period.

The effects of regular aerobic exercise in adolescent period on hippocampal neuron density, apoptosis and spatial memory.

It is known that positive effects of regular aerobic exercise on cognitive functions in humans and also animals; but how to the effects of aerobic exercise in adolescent period is unknown. The present study examined the effects of regular aerobic exercise on spatial memory using the Morris water maze, cell density and apoptosis of hippocampus in adolescent rats. Twenty-two days of age male rats were run on a treadmill for 30 min/session at a speed of 8m/min and 0 degrees slope, five times a week for 8 weeks. The present study showed that exercise induced significant cognitive improvement throughout brain maturation in rats. The number of hippocampal CA1 and CA3 neurons, and gyrus dentatus neurons were significantly increased in the exercised rats. There was no significant difference of CA2 neuron density between exercise and control groups. There was no significantly differences in any groups according to the results of apoptosis that account of TUNEL positive cells. The present results suggest that regular moderate aerobic treadmill exercise benefit in cognitive functions. This result may derive from treadmill exercise-induced increase cell density without altering of apoptosis in the hippocampus and dentate gyrus of 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-ß) are important neurotrophic factors for male reproductive system. OBJECTIVE: We aimed to investigate the correlation between testicular damage and testicular VEGF and NGF-ß 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-ß 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 Johnsen's 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-ß were decreased in diabetic testes. Correlation between VEGF and NGF-ß levels was strong. CONCLUSION: These results suggest that the decrease of VEGF and NGF-ß levels is associated with the increase of the apoptosis and testicular damage in diabetic rats. Testis VEGF and NGF-ß levels could be potential novel biomarkers for diabetes induced testicular damage.

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.

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.

Serum IGF-1 levels correlate negatively to liver damage in diabetic rats.

Diabetes and insulin resistance frequently cause liver damage. Diabetes also causes reduction in liver and blood IGF-1 levels. We investigated the relation between liver damage and IGF-1 levels in diabetic rats. Fourteen Wistar albino rats were divided into control and diabetic groups. Diabetes was induced by streptozotocin. Rats were sacrificed for biochemical and histologic examinations 2 weeks after streptozotocin injection. Serum and liver IGF-1 levels were decreased, liver malondialdehyde (MDA) levels were increased, glutathione peroxidase (GPx) enzymes activities were decreased and serum alanine aminotransferase (ALT) levels were increased in diabetic group. Microscopic examination of liver revealed that normal tissue organization was disrupted in streptozotocin-induced diabetic rats. There was a strongly positive correlation between blood glucose levels and liver injury, and blood and liver IGF-1 levels. There was a strongly negative correlation between blood IGF-1 levels and hepatic injury. Our results suggest that reduction of blood IGF-1 levels correlates with hepatic injury and circulating IGF-1 levels may have predictive value for determining hepatic damage that results from diabetes. In addition, circulating IGF-1 levels are correlated with glutathione levels and the oxidative stress status of diabetic rat liver.

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.