High-intensity interval training ameliorates spatial and recognition memory impairments, reduces hippocampal TNF-alpha levels, and amyloid-beta peptide load in male hypothyroid rats.

Thyroid hormones are critical for healthy brain functions at every stage of life. Hypothyroidism can cause severe cognitive dysfunction in patients who do not receive adequate treatment. Although thyroid hormone replacement alleviates cognitive decline in hypothyroid patients, there are studies showing that there is no complete recovery. The aim of this study was to investigate the effects of high-intensity interval training (HIIT) in hypothyroid rats on spatial and recognition memory, neuroinflammation, amyloid-beta load and compare these effects with T3 replacement. Hypothyroidism was induced and maintained by administration of 6-n-propyl-2-thiouracil (PTU) with their drinking water to 6-weeks-old male Sprague-Dawley rats for 7 weeks. The animals exercised in the treadmill according to the HIIT protocol for four weeks. T3 was injected intraperitoneally daily during the last two weeks of the study. All animals performed in the elevated plus maze test, Morris water maze test, novel object recognition test, and rotarod motor performance test in the last week of the study and then the animals were sacrificed. Amyloid beta (1-42) and TNFα levels were measured in the prefrontal cortex and hippocampus by ELISA. Anxiety-like behaviors did not significantly differ between groups. T3 replacement with or without HIIT increased motor performance in PTU-treated rats. HIIT and/or T3 replacement increased the exercise performance. HIIT and/or T3 replacement alleviated spatial and recognition memory impairments and normalized TNFα and amyloid-beta levels in the hippocampus in hypothyroid rats. In summary, regular physical exercise may have potential benefits in preserving cognitive functions in hypothyroid patients.

An overview of the currency and usefulness of behavioral tests used from past to present to assess anxiety, social behavior and depression in rats and mice.

Various tests have been developed to evaluate behavior in animal studies where rodents are used as animal models. These tests are useful for understanding the pathophysiology of many neuropsychiatric disorders such as anxiety, depression, autism spectrum disorder, and obsessive-compulsive disorder and examining potential treatments for these disorders. The use of behavioral tests is becoming popular day by day, and studies to improve and develop these tests are still ongoing. It is very important to select the appropriate test, consider the factors that may affect the experimental design, and use different tests that will support each other when necessary. In this review, we aimed to provide researchers an overview of the currency, usefulness, and frequency of use of various behavioral tests used from past to present in the evaluation of anxiety-like behavior, depression-like behavior, and social behavior in rodents.

The relationship between cognition, depression, fatigue, and disability in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic, progressive, and neurodegenerative central nervous system disorder. MS usually causes disability, cognitive deficiency, fatigue, and depression symptoms. OBJECTIVES: To assess cognitive functions of people with MS (pwMS) and investigate the impact of depression, fatigue, and disability on cognitive functions. METHODS: We administered the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery to assess 200 pwMS. The Expanded Disability Status Scale (EDSS) was used to evaluate disability levels. Fatigue Severity Scale (FSS) and the Beck Depression Inventory (BDI) were used, respectively, for fatigue and depression levels. RESULTS: EDSS and FSS scores were significantly higher in those with a disease duration of 5 years or more. Those with the EDSS ≥ 4 were found to have lower BICAMS performances and higher FSS scores. There was a significant difference in Symbol Digit Modalities Test (SDMT) performances between the groups with and without fatigue (FSS ≥ 4 and FSS < 4, respectively). When depression and fatigue symptoms concur or in the existence of just one of them or none of them, significant differences in terms of SDMT performances have been shown. CONCLUSION: The level of disability and fatigue adversely affects the cognitive functions of pwMS; depression has no significant effect. BICAMS that is specific for MS can be beneficial to assess the cognitive state of pwMS.

Prevalence of premenstrual syndrome and its relationship to depressive symptoms in first-year university students.

OBJECTIVES: To determine the prevalence of and factors influencing premenstrual syndrome (PMS) in first-year students at a university health campus and to evaluate the relationship between depression and PMS. Methods: This cross-sectional study was conducted on a population of 618 university students from March to June 2016 at Dokuz Eylül University, Izmir, Turkey. Data were collected using the Premenstrual Syndrome Scale (PMSS), Beck Depression Inventory and Student Identification Form. The data were analyzed with Version 20.0 of the Statistical Package for the Social Science. Descriptive statistics, Pearson's chi-square test, and Chi-square test for trend, and independent samples t test and logistic regression analysis were used. Results: The prevalence of PMS in the university students was 58.1%. Premenstrual syndrome was significantly higher in students who smoked, drink alcohol, and consumed a large amount of fatty and high-calorie foods, in students who had a bad to very bad perception of their economic situation, and those who had any chronic disease or anemia (p less than 0.05). Premenstrual syndrome was significantly higher in students who had a risk of depression (p less than 0.01). A statistically significant relationship was determined between the risk of depression and PMSS total score and all PMSS subscale scores except for appetite changes (p less than 0.01). Conclusion: Premenstrual syndrome was found in more than half of the students who participated in the study. Premenstrual syndrome was higher in students who had a chronic disease and/or an unhealthy lifestyle. There was a statistically significant relationship between PMS and risk of depression. Students who have PMS symptoms should be evaluated for the risk of depression.

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.

Determination of Factors Affecting Physical Activity Status of University Students on a Health Sciences Campus.

Upon graduation, students studying in departments related to health will work in the health sector and will guide and enlighten people with their knowledge and behavior. The purpose of this study was to determine the factors affecting the physical activity (PA) conditions of university students on a health sciences campus. A cross-sectional study was carried out on 706 students in a Turkish university. The data was obtained from a survey prepared by the researchers. The 26-question survey aimed to discover the students' socio-demographic characteristics and their awareness and practices concerning PA. We found that 30% of the students engage in some type of PA during their university education. A relationship was observed concerning their current PA and their family inactivity levels, as well as between inactivity before entering the university and inactivity during their education. The presence of a chronic disease in family members does not affect student PA. A majority of the students believe PA is beneficial (98.7%), 93.9% believe it relieves stress, and 94.5% believe it helps control body weight. Although students of medicine and related disciplines are aware of the importance of proper diet and adequate levels of PA in health, they did not implement theory into practice. Thus, it is questionable how young health professionals will promote the positive effects and necessity of regular physical activity if they do not apply these activities to their own lifestyle.

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.

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.

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.

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.

Anxiety caused by traumatic brain injury correlates to decreased prefrontal cortex VEGF immunoreactivity and neuron density in immature rats.

AIM: Traumatic brain injury (TBI) may cause neuropsychiatric disorders such as anxiety disorder which has negative effects on cognitive functions and behavior. The aim of this study is to investigate the effects of TBI on anxiety and vascular endothelial growth factor (VEGF) immunoreactivity on the prefrontal cortex of immature rats, which is one of the anxiety-related regions of the brain in 7-day-old immature rats subjected to contusion injury. MATERIAL and METHODS: Rats were divided into three groups: Control (n=7), Sham (n=7) and TBI (n=7). Anxiety levels were assessed with open field activity and elevated plus maze in postnatal 27 days. Prefrontal cortex damage related to TBI was examined by cresyl violet staining and VEGF immunostaining. Prefrontal cortex neuronal density was calculated. Serum corticosterone levels were determined. RESULTS: The anxiety level in the TBI group was significantly greater than the control and sham groups. The prefrontal cortex VEGF immunostaining score and neuron density were decreased in the TBI group compared to control and sham group. Serum corticosterone levels were significantly increased in the TBI group. CONCLUSION: These results indicate that TBI decreases VEGF immunoreactivity in prefrontal cortex neurons and increases the anxiety levels of immature rats.

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 offspring's 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.

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.

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 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 mother's 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.

Effects of maternal deprivation on melatonin production and cognition in adolescent male and female rats.

OBJECTIVES: It is known that maternal deprivation (MD) may alter cognitive functions such as learning and memory in adult life by effecting normal growth and development. However, the mechanisms of these cognitive alterations are unknown. The aim of this study is to investigate the effects of maternal deprivation on cognition and melatonin production in adolescent male and female rats. METHODS: The litters were separated daily from their mothers for 6 hours on postnatal days 2 to 20. The spatial memory performance was evaluated using a Morris water maze between the postnatal 26th and 32nd days. Plasma melatonin levels were determined on postnatal days 42. RESULTS: MD-rats had longer escape latencies at the second, third and fifth days of training days and spend significantly less time in probe trial, compared to control animals. MAIN FINDINGS: The repeated maternal deprivation caused low blood melatonin levels and there was a significant negative correlation between blood melatonin levels and spatial memory performance in both of male and female adolescent rats. CONCLUSION: These results suggest an association between melatonin production and neurodevelopment. Further studies are needed to determine the interaction between maternal deprivation and pineal gland maturation/function.

Effects of sprint exercise on oxidative stress in skeletal muscle and liver.

Although numerous studies have tested the effects of continuous exercise regimens on antioxidant defences, information on the effect of sprint exercise on the antioxidant defence system and lipid peroxidation levels of tissues is scant. The present study was designed to determine the effects of sprint exercise on the lipid peroxidation and antioxidant enzyme system in liver and skeletal muscle during the post-exercise recovery period in untrained mice. Mice performed 15 bouts of exercise, each comprising running on a treadmill for 30 s at 35 m.min(-1) and a 5 degrees slope, with a 10-s rest interval between bouts. They were then killed by cervical dislocation either immediately (0 h), 0.5 h, 3 h or 24 h after completion of the exercise. Their gastrocnemius muscle and liver tissues were quickly removed. It was found that blood lactate levels increased immediately after the exercise, but had returned to control levels by 0.5 h post-exercise. This exercise regimen had no effect on the activity of superoxide dismutase and glutathione peroxidase in these tissues. Levels of muscle thiobarbituric acid reactive substances (TBARS) had increased at 0.5 and 3 h post-exercise, and then returned to control levels by 24 h post-exercise. In conclusion, acute sprint exercise in mice resulted in an increase in TBARS levels in skeletal muscle; no change was observed in the liver. Antioxidant enzyme activities remained unaffected by acute sprint exercise in these tissues.