Elizabeth Teodorov

Acute Aerobic Exercise Increases Brain-Derived Neurotrophic Factor Levels in Elderly with Alzheimer's Disease

Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimers disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity.

Ethanol-induced sensitization depends preferentially on D1 rather than D2 dopamine receptors

Behavioral sensitization, defined as a progressive increase in the locomotor stimulant effects elicited by repeated exposure to drugs of abuse, has been used as an animal model for drug craving in humans. The mesoaccumbens dopaminergic system has been proposed to be critically involved in this phenomenon; however, few studies have been designed to systematically investigate the effects of dopaminergic antagonists on development and expression of behavioral sensitization to ethanol in Swiss mice. We first tested the effects of D(1) antagonist SCH-23390 (0-0.03 mg/kg) or D(2) antagonist Sulpiride (0-30 mg/kg) on the locomotor responses to an acute injection of ethanol (2.0 g/kg). Results showed that all tested doses of the antagonists were effective in blocking ethanols stimulant effects. In another set of experiments, mice were pretreated intraperitoneally with SCH-23390 (0.01 mg/kg) or Sulpiride (10 mg/kg) 30 min before saline or ethanol injection, for 21 days. Locomotor activity was measured weekly for 20 min. Four days following this pretreatment, all mice were challenged with ethanol. Both antagonists attenuated the development of ethanol sensitization, but only SCH-23390 blocked the expression of ethanol sensitization according to this protocol. When we tested a single dose (30 min before tests) of either antagonist in mice treated chronically with ethanol, both antagonists attenuated ethanol-induced effects. The present findings demonstrate that the concomitant administration of ethanol with D(1) but not D(2) antagonist prevented the expression of ethanol sensitization, suggesting that the neuroadaptations underlying ethanol behavioral sensitization depend preferentially on D(1) receptor actions.

Physical exercise and vascular endothelial growth factor (VEGF) in elderly: A systematic review

UNLABELLEDnThe aim of this study was to conduct a systematic review of studies that verified the effects of physical exercise on vascular endothelial growth factor (VEGF) in elderly.nnnMETHODOLOGYnThe bibliographic search was conducted in five database, from 1990 to 2013, with the following keywords and boolean operators: physical exercise OR physical exercise OR physical therapy OR exercise OR training AND VEGF OR vascular endothelial growth factor AND aged OR older OR elderly. The inclusion criteria were: (1) sample including elderly with average age of 60; (2) studies that verified the effects of acute exercise; (3) studies that verified the effects of chronic physical exercise; (4) studies with humans; (5) randomized controlled trials, randomized non-controlled trials, non-randomized controlled trials, non-randomized and non-controlled trials; (6) assessment of VEGF peripheral concentrations.nnnRESULTSnTen studies were selected, and that four of them verified an increase of VEGF concentrations after practicing physical exercise and six studies did not verify any change on VEGF concentrations.nnnCONCLUSIONnDifferent populations found in this study and the different exercise protocols applied in the studies of this review make it difficult to establish parameters of what would be the best type of exercise to promote an increase on the concentrations of VEGF in the elderly. Therefore, we suggest that further studies can be performed, so that we can establish some recommendations for this population.

Enhancement of behavioral sensitization, anxiety-like behavior, and hippocampal and frontal cortical CREB levels following cocaine abstinence in mice exposed to cocaine during adolescence.

Adolescence has been linked to greater risk-taking and novelty-seeking behavior and a higher prevalence of drug abuse and risk of relapse. Decreases in cyclic adenosine monophosphate response element binding protein (CREB) and phosphorylated CREB (pCREB) have been reported after repeated cocaine administration in animal models. We compared the behavioral effects of cocaine and abstinence in adolescent and adult mice and investigated possible age-related differences in CREB and pCREB levels. Adolescent and adult male Swiss mice received one daily injection of saline or cocaine (10 mg/kg, i.p.) for 8 days. On day 9, the mice received a saline injection to evaluate possible environmental conditioning. After 9 days of withdrawal, the mice were tested in the elevated plus maze to evaluate anxiety-like behavior. Twelve days after the last saline/cocaine injection, the mice received a challenge injection of either cocaine or saline, and locomotor activity was assessed. One hour after the last injection, the brains were extracted, and CREB and pCREB levels were evaluated using Western blot in the prefrontal cortex (PFC) and hippocampus. The cocaine-pretreated mice during adolescence exhibited a greater magnitude of the expression of behavioral sensitization and greater cocaine withdrawal-induced anxiety-like behavior compared with the control group. Significant increases in CREB levels in the PFC and hippocampus and pCREB in the hippocampus were observed in cocaine-abstinent animals compared with the animals treated with cocaine in adulthood. Interestingly, significant negative correlations were observed between cocaine sensitization and CREB levels in both regions. These results suggest that the behavioral and neurochemical consequences of psychoactive substances in a still-developing nervous system can be more severe than in an already mature nervous system.

Plasticity of Opioid Receptors in the Female Periaqueductal Gray: Multiparity-Induced Increase in the Activity of Genes Encoding for Mu and Kappa Receptors and a Post-Translational Decrease in Delta Receptor Expression

The periaqueductal gray (PAG) has been reported as a potential site for opioid regulation of behavioral selection. Opioid-mediated behavioral and physiological responses differ between nulliparous and multiparous females. This study addresses the effects of multiple reproductive experiences on μ-, κ- and δ-opioid receptor (Oprm1, Oprk1, and Oprd1 respectively) gene activity and μ, κ and δ protein expression (MOR, KOR and DOR respectively) in the PAG of the female rats. This was done by evaluating the opioid gene expression using real-time (RT-PCR) and quantification of each protein receptor by Western blot analysis. The RT-PCR results show that multiple reproductive experiences increase Oprm1 and Oprk1 gene expression. Western blot analysis revealed increased MOR and KOR while DOR protein was decreased in multiparous animals. Taken together, these data suggest that multiple reproductive experiences influence both gene activity and opioid receptor expression in the PAG. Post-translational mechanisms seem particularly relevant for DOR expression. Thus, opioid transmission in the PAG might be modulated by different mechanisms of multiparity-induced plasticity according to the opioid receptor type.

Influence of chronic exercise on serum cortisol levels in older adults

The circulating level of cortisol is regulated by the hypothalamic-pituitary-adrenal axis through a neuroendocrine feedback circuit. This circuit can be activated by physiological stimuli such as stress, diseases, and exercise. High levels of serum cortisol hormone normally occur as a byproduct of aging, and can cause several types of damage to the organism and exacerbate immunosenescence. There is a great deal of variability in the cortisol response with regard to type, intensity, volume, and frequency of exercise. However, these relationships have been extensively studied with respect to the acute effects of exercise. Despite the well-known effects of acute exercise on cortisol response, it is unclear how it is affected by chronic exercise and the aging process. Therefore, the aim of this study was to conduct a review of studies that attempt to analyze the influence of chronic exercise on serum cortisol hormone in older people. In order to accomplish this goal, a review from 1970 to June 2012 period was performed using the following databases: Biological Abstracts, PsycINFO, PubMed/Medline, and the Web of Science. Eight articles met the criteria used in this study. Based on the included articles, chronic exercise may influence the serum levels of cortisol levels in older people. Despite this evidence, these results may not be generalized to the entire population of older people, given the few number of studies and especially because the studies showed diversity in variables and methodologies.

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250u2005g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15u2005mg/kg, sc) or 0.9% saline (up to 1u2005mL/kg) and after 30u2005min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of U69593 group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female reproduction.

Treatment with steroid hormones and morphine alters general activity, sexual behavior, and opioid gene expression in female rats

AIMSnPrevious studies have shown that brain opioid peptides exert an inhibitory influence on gonadotropin secretion. Different types of brain opioids, such as β-endorphin, enkephalin, and dynorphin, exert their actions by binding to specific opioid receptors (i.e., μ, δ, and κ, respectively). The present study determined the effects of chronic treatment with morphine in female rats with pharmacologically induced estrus on behavior and opioid receptor gene and protein expression in the hypothalamus, striatum, and periaqueductal gray.nnnMAIN METHODSnFemale ovariectomized rats treated with estrogen+progesterone received 3.5mg/kg morphine once per day for 6days. We evaluated general activity, sexual behavior, Oprm1, Oprd1, and Oprk1 gene expression, and μ opioid receptor (MOR), δ opioid receptor (DOR), and κ opioid receptor (KOR) protein expression in the hypothalamus, striatum, and periaqueductal gray in adult virgin female ovariectomized rats.nnnKEY FINDINGSnChronic morphine treatment increased locomotion and grooming behavior, decreased immobility time, decreased sexual behavior, and decreased the lordosis quotient. The molecular biology results showed that morphine treatment increased Oprm1 gene and MOR protein expression in the striatum and decreased KOR protein expression in the hypothalamus in animals that were assessed for general activity. The animals that were evaluated for sexual behavior exhibited an increase in Oprm1 expression in the periaqueductal gray and increase in KOR expression in the striatum.nnnSIGNIFICANCEnThese results suggest that both opioid system activation and sex hormones alter behavioral and molecular patterns in ovariectomized rats within a relatively short period of time.

Role of steroid hormones and morphine treatment in the modulation of opioid receptor gene expression in brain structures in the female rat

This study determined the effects of acute treatment with morphine on the expression of the Oprm1, Oprk1, and Oprd1 genes (which encode μ, κ, and δ receptors, respectively) in the striatum, hypothalamus, and periaqueductal gray (PAG) in ovariectomized female rats treated with estrogen. Ovariectomized female rats were divided into five equal groups. Two groups received estrogen (50xa0µg/kg, 54xa0h before testing) and saline (ES group) or 3.5xa0mg/kg morphine (EM group) 2xa0h before euthanasia. The SS group received saline solution 54 and 2xa0h before the experiments. The SM group received saline 54xa0h and 3.5xa0mg/kg morphine 2xa0h before the experiments. The W group remained undisturbed. The genes expression were evaluated. Oprm1 and Oprk1 expression were activated, respectively, in the hypothalamus and PAG and in the striatum and PAG by morphine only in estrogen-treated animals. Oprd1 expression in the hypothalamus and PAG was activated by morphine in both estrogen-treated and -nontreated animals. The Oprm1 and Oprk1 gene response to morphine might depend on estrogen, whereas the Oprd1 gene response to morphine might not depend on estrogen, supporting the hypothesis of a functional role for ovarian hormones in opioid receptor-mediated functional adaptations in the female brain.