The ameliorative effect of midazolam on empathy-like behavior in old rats.

Although studies suggest that cognitive functions in the elderly are impaired, elderly people tend to be more successful and wiser in solving emotional problems. In empathy-like behavior models, the observer rat rescues the distressed cage mate by displaying emotional and cognitive ability. The aim of the study was to investigate the changes in empathy-like behavior in older rats in comparison to adult rats. In addition, we wanted to determine the effects of alterations in neurochemicals (such as corticosterone, oxytocin, vasopressin, and their receptor levels) and emotional situations on this behavior. In our study, we initially completed empathy-like behavior tests and emotional tests (open field, elevated plus maze) and performed neurochemical examinations in the serum and brain tissues. In the second step of research, we applied a midazolam (benzodiazepine) treatment to examine the effect of anxiety on empathy-like behavior. In the old rats, we observed that empathy-like behavior deteriorated, and anxiety signs were more pronounced. We detected a positive correlation between the latency in empathy-like behavior and corticosterone levels and v1b receptor levels. The midazolam effect on empathy-like behavior was attenuated by flumazenil (a benzodiazepine receptor antagonist). The recordings of ultrasonic vocalization showed frequencies around 50 kHz emitted by the observer and this was associated with the expectation of social contact. Our results state that compared to adult rats, old rats were more concerned and failed during empathy-like behavior. Midazolam may improve this behavior by anxiolysis.

A combination of ketogenic diet and voluntary exercise ameliorates anxiety and depression-like behaviors in Balb/c mice.

The positive effects of both ketogenic diet (KD) and regular voluntary exercise on anxiety and depression behavior have been recently reported in rodent animals, but the effects of pairing a KD with exercise on depression and anxiety are unknown. In this study, we aimed to investigate the effects of combination of KD and regular voluntary exercise on anxiety and depression-like behavior in Balb/c mice. We've demostrated that anxiety and depression levels decreased in KD-exercised (KD-Ex) mice. ß-hydroxybutyrate (BHB) levels increased while glucose, insulin levels and LDL/HDL ratio decreased in KD-Ex mice. There was a negative correlation between BHB and the time spent in the closed arms of elevated plus maze (EPM) or the time spent in periphery walls of open field test (OFT) and the immobility time in forced swim test (FST) which all of them are indicators of low depression and anxiety levels. There was a positive correlation between LDL/HDL ratio and the time spent in the closed arms of EPM or the immobility time in FST. The immobility time in FST was positively correlated with insulin while the mobility time in FST was negatively correlated with glucose. In conclusion, these results suggest that decline in anxiety and depression-like behaviors resulted from KD with regular voluntary exercise may be associated with increased BHB levels and decreased LDL/HDL ratio and insulin or glucose levels. Further research is necessary for our understanding of the mechanisms by which pairing a KD with voluntary exercise influences brain and behavior.

Regular aerobic exercise increased VEGF levels in both soleus and gastrocnemius muscles correlated with hippocampal learning and VEGF levels.

Physical exercise improves learning and memory abilities by increasing the levels of several growth factors in the hippocampus. One growth factor, vascular endothelial growth factor (VEGF), is primarily produced in the muscles and not only increases in the periphery during exercise but can also cross the blood-brain barrier. The aim of this study is to investigate the effects of regular aerobic chronic exercise on different types of muscle fibers and the relationships between learning/memory and muscle induced-VEGF. Following a one-week adaptation period, male rats underwent treadmill training at a speed of 8 m/min for 30 min daily, 3 days a week for 6 weeks. Memory functions were evaluated using the Morris water maze. VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were measured in type 1 and type 2 muscle fibers and VEGF levels were also measured in the hippocampus. Exercise positively affected both learning and memory and also increased VEGF levels in both muscle fiber types. Muscle VEGF levels positively correlate with hippocampal learning and hippocampal VEGF levels. Exercise reduced both SOD and MDA levels in type 1 and type 2 muscle fibers, whereas GPx levels decreased only in type 2 muscle fibers. Our findings suggest that regular aerobic exercise elevates VEGF levels and diminishes oxidative stress in both fiber types. Exercise-induced VEGF levels in both type 1 and 2 muscle fibers appear to be associated with the positive effect of exercise on learning and memory function and is accompanied by an increase in VEGF levels in the hippocampus. Further research is needed to elucidate the exact mechanism by which fiber type-specific VEGF mediates hippocampal neurogenesis and angiogenesis.Physical exercise improves learning and memory abilities by increasing the levels of several growth factors in the hippocampus. One growth factor, vascular endothelial growth factor (VEGF), is primarily produced in the muscles and not only increases in the periphery during exercise but can also cross the blood-brain barrier. The aim of this study is to investigate the effects of regular aerobic chronic exercise on different types of muscle fibers and the relationships between learning/memory and muscle induced-VEGF. Following a one-week adaptation period, male rats underwent treadmill training at a speed of 8 m/min for 30 min daily, 3 days a week for 6 weeks. Memory functions were evaluated using the Morris water maze. VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were measured in type 1 and type 2 muscle fibers and VEGF levels were also measured in the hippocampus. Exercise positively affected both learning and memory and also increased VEGF levels in both muscle fiber types. Muscle VEGF levels positively correlate with hippocampal learning and hippocampal VEGF levels. Exercise reduced both SOD and MDA levels in type 1 and type 2 muscle fibers, whereas GPx levels decreased only in type 2 muscle fibers. Our findings suggest that regular aerobic exercise elevates VEGF levels and diminishes oxidative stress in both fiber types. Exercise-induced VEGF levels in both type 1 and 2 muscle fibers appear to be associated with the positive effect of exercise on learning and memory function and is accompanied by an increase in VEGF levels in the hippocampus. Further research is needed to elucidate the exact mechanism by which fiber type-specific VEGF mediates hippocampal neurogenesis and angiogenesis.

The Chronic Use of Magnesium Decreases VEGF Levels in the Uterine Tissue in Rats.

Vascular endothelial growth factor (VEGF) is the most important regulator of angiogenesis which serves to provide sufficient blood supply, and can trigger both physiological and pathological angiogenesis. Recent studies have shown that VEGF increases in gynecological diseases (such as endometriosis, ovarian, and endometrial cancers) and is a prognostic factor in these pathologies. Therefore, VEGF should be maintained at appropriate levels. Magnesium is used in many gynecological practices (such as eclampsia, preeclampsia, dysmenorrhea, and climacteric symptoms) and the mechanisms of action are still under investigation. Redox status, which can be regulated by magnesium, was shown to affect VEGF expression. The aim of this study was to evaluate the effects of chronic magnesium use on VEGF and oxidative status in the uterus. Magnesium sulfate was administered to rats at doses of 30 mg/kg (intramuscular) for 2 weeks. VEGF, Superoxide dismutase (SOD), Glutathione peroxidase (GPx), and Malondialdehyde (MDA) levels were measured using ELISA; vascular and cellular alterations were determined by histology in the uterine tissue at the metoestrus phase. In the uterine tissue of Mg-treated subjects, magnesium levels increased while VEGF, SOD, GPx, and MDA levels decreased without histological changes. There was a negative correlation between uterine tissue magnesium levels and VEGF, SOD, GPx, and MDA levels. Consequently, the results of this study demonstrated that regular magnesium use decreased VEGF levels in uterus. Decreased VEGF levels were associated with decreased uterine oxidative stress. Chronic magnesium usage may protect the uterine tissue from certain diseases in which angiogenesis is critical.

Mild-intensity Exercise Triggers VEGF in the Digestive Tract Via Both Hypoxic and Nonhypoxic Mechanisms

Abstract Hypoxia occurs in the splanchnic region during exercise associated with sympathetic activity. In the elderly, vascular insufficiency and low vascular endothelial growth factor (VEGF) expression are observed. Compared to young people, sympathetic signals of older individuals are blunted and more resistant to splanchnic blood flow alterations during exercise. VEGF induces vasodilation responses and hence may retain blood in the splanchnic vascular bed. We hypothesized that regular mild-intensity exercise triggers weak VEGF expression in the digestive tract of the elderly. The effects of exercise on the levels of VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) in the stomach, jejunum, ileum and colon tissues were evaluated. With exercise, the VEGF levels in the stomach and colon increased. Although the SOD, GPx, and MDA levels decreased in the stomach, they increased in the colon. T-AOC increased in the stomach and there was no change in the jejunum, ileum and colon. The hypoperfusion during exercise was not equal in all regions of the gastrointestinal tract in the aged subjects. Hypoxia and other exercise-related mechanisms could have led to this VEGF induction. The stomach, jejunum, and ileum might have developed resistance to ischemia. The induction of VEGF may be beneficial in aging-associated impaired gastrointestinal homeostasis and neovascularization.

Gene expression of pro-opiomelanocortin and melanocortin receptors is regulated in the hypothalamus and mesocorticolimbic system following nicotine administration.

Pro-opiomelanocortin (POMC)-derived peptides and their receptors have been shown to play important roles in natural and drug-induced reward and reinforcement. Reward process may involve the regulation of POMC gene expression and the gene expression of POMC-derived peptide receptors. The present study investigated the alterations observed in the transcript levels of POMC, melanocortin 3 (MC3R), melanocortin 4 (MC4R) and mu-opioid receptors (MOR) in the hypothalamus and mesocorticolimbic system during nicotine exposure. Rats were injected subcutaneously for 5days with one of the three doses (0.2, 0.4 or 0.6mg/kg/day, free base) of nicotine and were decapitated one hour after a challenge dose on the sixth day. mRNA levels of POMC in the hypothalamus, MC3R in the ventral tegmental area (VTA), MC4R and MOR in the medial prefrontal cortex (mPFC), nucleus accumbens, dorsal striatum, amygdala, lateral hypothalamic area and VTA were measured by quantitative real-time PCR. Our results showed that treatment with 0.6mg/kg/day nicotine upregulated POMC mRNA in the hypothalamus and MC4R mRNA in the mPFC. Additionally, all three nicotine doses increased MC3R mRNA expression in the VTA. On the other hand, none of the nicotine doses altered MOR mRNA levels in the mesocorticolimbic system and associated limbic structures. These results suggest that nicotine may enhance melanocortin signaling in the mesocorticolimbic system and this alteration may be an important mechanism mediating nicotine reward.