Activity-related Effects Research Articles

Analysis of the gut microbiome in sled dogs reveals glucosamine- and activity-related effects on gut microbial composition.

The composition of the microbiome influences many aspects of physiology and health, and can be altered by environmental factors, including diet and activity. Glucosamine is a dietary supplement often administered to address arthritic symptoms in humans, dogs, and other mammals. To investigate how gut microbial composition varies with glucosamine supplementation, we performed 16S rRNA sequence analysis of fecal samples from 24 Alaskan and Inuit huskies and used mixed effects models to investigate associations with activity, age, and additional factors. Glucosamine ingestion, age, activity, sex, and diet were correlated with differences in alpha-diversity, with diversity decreasing in dogs consuming glucosamine. Beta-diversity analysis revealed clustering of dogs based on glucosamine supplementation status. Glucosamine supplementation and exercise-related activity were associated with greater inter-individual pairwise distances. At the family level, Lactobacillaceae and Anaerovoracaceae relative abundances were lower in supplemented dogs when activity was accounted for. At the genus level, Eubacterium [brachy], Sellimonus, Parvibacter, and an unclassified genus belonging to the same family as Parvibacter (Eggerthellaceae) all were lower in supplemented dogs, but only significantly so post-activity. Our findings suggest that glucosamine supplementation alters microbiome composition in sled dogs, particularly in the context of exercise-related activity.

Content validity of the Scoliosis Research Society questionnaire (SRS-22r): A qualitative concept elicitation study.

Scoliosis Research Society-22 revised (SRS-22r) is the common questionnaire used to evaluate health related quality of life (HRQOL) for young people with adolescent idiopathic scoliosis (AIS). The aim of this study is to evaluate its content validity for this population. In-depth semi-structured interviews were conducted with a purposive sample of young people with AIS (Cobb angle ≥25˚, aged 10-18 years). Concept elicitation was used to evaluate the influence of AIS on participants' HRQOL. Participant information sheets and consent/assent forms were age relevant. Topic guide was informed by the SRS-22r and existing evidence. Interviews were audio and video recorded, transcribed verbatim, coded, and analysed using thematic analysis. Derived themes/codes were compared with SRS-22r contents (domains/items). Eleven participants (mean age 14.9 years [SD = 1.8]; 8 female) were recruited. The mean curve size was 47.5° [SD = 18°] and participants had been managed via different approaches. Four main themes emerged with associated subthemes: 1) Physical effects related to physical symptoms (back hurt, stiffness) and body asymmetry (uneven shoulders), 2) Activity-related effects showed impact on mobility (sitting for long periods), self-care (dressing), and school activities (focus during lessons), 3) Psychological effects revealed emotional (feel worried), mental (sleep quality), and body image effects (hide back from others), 4) Social effects (participation in school and leisure activities), and school, friends and mental health support. A weak association was found between items of the SRS-22r and the identified codes. The SRS-22r does not adequately capture important concepts that relate to HRQOL of adolescents with AIS. These findings support revision of the SRS-22r, or the development of a new patient reported outcome measure to evaluate HRQOL of adolescents with AIS.

The effect of web-based family-centered empowerment program in preventing the risk factors of substance abuse in students' parents; application of the health promotion model.

The age of onset of substance abuse among adolescents has recently decreased worldwide. Parents play an important role in preventing their children from drug abuse. This study aimed to investigate the effect of web-based family-centered empowerment program in preventing the risk factors of substance abuse in students' parents, using the health promotion model (HPM). This interventional study was based on 118 parents of high school students in Sabzevar, Iran (2019). Multi-stage random sampling was used to divide the participants into the experimental (n = 65) and control (n = 65) groups. The data were collected through a researcher-made questionnaire based on Pender's HPM. A website was designed to perform all stages of the study. The web-based educational intervention was performed for the experimental group. Both groups completed the questionnaires 2 months after the educational intervention. The data were analyzed using t-test, paired t-test, regression, correlation, and analysis of covariance. There was a significant difference between the scores of prior related behavior, perceived benefits of action, activity-related effect, situational influences, competitors, and commitment in the parents of the experimental group compared to the control group after the educational intervention (P-value < 0.05). Moreover, a significant difference was observed between preventive behaviors of substance abuse and the mean score of perceived barriers to action, perceived self-efficacy, interpersonal influences, and role model in the parents of the experimental group compared to the control group after the educational intervention (P-value < 0.05). Overall, designing an educational intervention based on the constructs of Pender's HPM could be an effective strategy for promoting preventive behaviors of substance abuse in parents.

Efficacy of Pender's Health Promotion-based Model on Intervention for Enhancing University of Mosul Hypertensive Employees' Eating Behaviors: A Randomized Controlled Trial

Dietary habits are an essential lifestyle element contributing to hypertension development and can be changed if adequately controlled and educated. The DASH (Dietary Approaches to Stop Hypertension) diet, which emphasizes consuming fruits, vegetables, and low-fat dairy products, is recommended to lower blood pressure and reduce sodium intake. The article aims to identify the Efficacy of Pender's Health Promotion-based Model on Intervention for Enhancing University of Mosul Hypertensive Employees' Eating Behaviors. A proper experimental design employing the randomized controlled trial approach is used to establish the efficiency of Pander's health promotion based on intervention for enhancing eating behaviors among University of Mosul hypertension personnel. The study was conducted at the University of Mosul from first December 2021 to the end of April 2022. The sample was selected from a homogeneous group of 220 employees. Random selection and random assignment are used to create the experimental and control group for every 25 employees. This study's results show statistically significant differences across all Pander Model principles connected to hypertension-associated eating behavior. On the other hand, the perceived barrier was the only belief that remained constant over time.The study indicated that the Pender model's health promotion demonstrates the relevance of hypertension prevention and has a favorable impact on employees' perceptions of perceived advantages, Self-efficacy, and perceived risks, social support and activity-related effect of unhealthy Hypertension advised employees to use their eating behavior through a healthy diet, physical activity and other healthy behaviors to hypertension control to prevent different health hazards, social support for activating "readiness" to break free from unhealthy habits and self-efficacy for self-assurance in blood pressure control. Keywords: Efficacy, Pender's Model, health promotion, Hypertensive Employees, Eating Behaviors

Inhibition of Cardiac RIP3 Mitigates Early Reperfusion Injury and Calcium-Induced Mitochondrial Swelling without Altering Necroptotic Signalling.

Receptor-interacting protein kinase 3 (RIP3) is a convergence point of multiple signalling pathways, including necroptosis, inflammation and oxidative stress; however, it is completely unknown whether it underlies acute myocardial ischemia/reperfusion (I/R) injury. Langendorff-perfused rat hearts subjected to 30 min ischemia followed by 10 min reperfusion exhibited compromised cardiac function which was not abrogated by pharmacological intervention of RIP3 inhibition. An immunoblotting analysis revealed that the detrimental effects of I/R were unlikely mediated by necroptotic cell death, since neither the canonical RIP3–MLKL pathway (mixed lineage kinase-like pseudokinase) nor the proposed non-canonical molecular axes involving CaMKIIδ–mPTP (calcium/calmodulin-dependent protein kinase IIδ–mitochondrial permeability transition pore), PGAM5–Drp1 (phosphoglycerate mutase 5–dynamin-related protein 1) and JNK–BNIP3 (c-Jun N-terminal kinase–BCL2-interacting protein 3) were activated. Similarly, we found no evidence of the involvement of NLRP3 inflammasome signalling (NOD-, LRR- and pyrin domain-containing protein 3) in such injury. RIP3 inhibition prevented the plasma membrane rupture and delayed mPTP opening which was associated with the modulation of xanthin oxidase (XO) and manganese superoxide dismutase (MnSOD). Taken together, this is the first study indicating that RIP3 regulates early reperfusion injury via oxidative stress- and mitochondrial activity-related effects, rather than cell loss due to necroptosis.

The Impact of the COVID-19 Pandemic on Independent Creative Activities in Two Large Cities in Romania.

The COVID-19 pandemic has had both financial and activity-related effects on a number of areas of activity, among which those involving the creative industries have proved to be weak in their capacity to survive the halting of all events held in physical spaces. The long-term effects of the current health crisis are bringing about changes in cultural demand and offer and highlighting the need to adapt and to think of new ways of functioning. Taking its cue from this situation, the research underlying our article set out to investigate the ways in which Romania’s independent creative sector is adapting. We achieved this by means of conducting 25 semi-structured interviews and undertaking case studies of two cities that are among the most effervescent from the point of view of cultural and creative industries, Timișoara and Cluj-Napoca. With the strengthening of this sector as the aim in view, the forms of early social resilience we identified are capable in the short term of taking action to ensure the survival of some of the spaces; in the medium term, through activating mechanisms that encourage entrepreneurial spirit, they will be able to adapt to any external shock.

Importance of performance status and physical activity in cancer patients

SummaryBackgroundThis review summarizes current data on the effects of exercise interventions and physical activity in cancer prevention, treatment and related side effect management, as well as on the rehabilitation of cancer patients.Patients and methodsThe overall quality of patient studies is still poor due to methodological limitations. Major limitations of the interventional exercise studies conducted include their designs, with regard to missing randomization or the absence of control groups, and the use of heterogeneous assessment methods to quantify and objectify physical activity. As a result, there are no specific exercise recommendations in cancer patients as yet that would essentially differ from exercise recommendations for healthy subjects. Nevertheless, due to major findings and empirical data, the field of research into exercise- and physical activity-related effects on disease and therapy-associated aspects is young and rapidly emerging.ConclusionExercise potentially contributes to the prevention and rehabilitation of cancer and represents a powerful tool in the prevention of various side effects under chemotherapy. Current data from interventional studies show preliminary positive effects for diverse movement programs and especially through specific combinations of endurance and resistance training. Additional randomized controlled trials with standardized assessments and controlling for potential confounders are needed to confirm and expand these findings.

Psychosocial determinants of self-care behavior in outpatients with heart failure: A test of Penderʼs health promotion model

Background: Patients with heart failure need to be engaged in adequate cardiac self-care behaviors helping to prevent the development of the disease and ameliorate their health status. However, the conceptual model of the present study has not been tested in previous studies among patients with heart failure. Objectives: The present study aimed to investigate the psychosocial determinants based on Pender’s health promotion model (HPM) affecting self-care behavior among outpatients suffering from heart failure. Methods: In this cross-sectional study, a total of 200 patients suffering from heart failure were selected from the outpatient clinics of Tabriz, Iran, using convenience sampling and assessed for self-self-care behaviors and major concepts of HPM via self-administered questionnaires. Path analysis was used in order to analyze the conceptual model Results: The present hypothetical model showed a good fit. Perceived benefits and activity-related effects directly affected self-care behaviors. Bootstrapping mediation analyses indicated that perceived self-efficacy, perceived barriers, perceived benefits, and activity-related effects indirectly affected self-care behaviors through commitment to action. Conclusions: The commitment to action can help to promote self-care behaviors among the subjects suffering from heart failure. The interventions should take the role of predictive variables of this study and commitment to action into account in these patients.

Human Resting Energy Expenditure Varies with Circadian Phase

There is emerging evidence that circadian misalignment may alter energy expenditure, leading to obesity risk among those with irregular schedules [1-5]. It has been reported that energy expenditure is affected by the timing of sleep, exercise, and meals [6]. However, it is unclear whether the circadian system also modulates energy expenditure, independent of behavioral state and food intake. Here, we used a forced desynchrony protocol to examine whether fasted resting energy expenditure (REE) varies with circadian phase in seven participants. This protocol allowed us to uncouple sleep-wake and activity-related effects from the endogenous circadian rhythm, demonstrating that REE varies by circadian phase. REE is lowest at circadian phase ∼0°, corresponding to the endogenous core body temperature (CBT) nadir in the late biological night, and highest at circadian phase ∼180° in the biological afternoon and evening. Furthermore, we found that respiratory quotient (RQ), reflecting macronutrient utilization, also varies by circadian phase. RQ is lowest at circadian phase ∼240° and highest at circadian phase ∼60°, which corresponds to biological morning. This is the first characterization of a circadian profile in fasted resting energy expenditure and fasted respiratory quotient (with rhythmic profiles in both carbohydrate and lipid oxidation), decoupled from effects of activity, sleep-wake cycle, and diet in humans. The rhythm in energy expenditure and macronutrient metabolism may contribute to greater weight gain in shift workers and others with irregular schedules.

Perinatal lead (Pb) exposure results in sex and tissue-dependent adult DNA methylation alterations in murine IAP transposons.

Epidemiological and animal data suggest that adult chronic disease is influenced by early-life exposure-induced changes to the epigenome. Previously, we observed that perinatal lead (Pb) exposure results in persistent murine metabolic- and activity-related effects. Using phylogenetic and DNA methylation analysis, we have also identified novel intracisternal A particle (IAP) retrotransposons exhibiting regions of variable methylation as candidate loci for environmental effects on the epigenome. Here, we now evaluate brain and kidney DNA methylation profiles of four representative IAPs in adult mice exposed to human physiologically relevant levels of Pb two weeks prior to mating through lactation. When IAPs across the genome were evaluated globally, average (sd) methylation levels were 92.84% (3.74) differing by tissue (P < 0.001), but not sex or dose. By contrast, the four individual IAPs displayed tissue-specific Pb and sex effects. Medium Pb-exposed mice had 3.86% less brain methylation at IAP 110 (P < 0.01), while high Pb-exposed mice had 2.83% less brain methylation at IAP 236 (P = 0.01) and 1.77% less at IAP 506 (P = 0.05). Individual IAP DNA methylation differed by sex for IAP 110 in the brain and kidney, IAP 236 in the kidney, and IAP 1259 in the kidney. Using Tomtom, we identified three binding motifs that matched to each of our novel IAPs impacted by Pb, one of which (HMGA2) has been linked to metabolic-related conditions in both mice and humans. Thus, these recently identified IAPs display tissue-specific environmental lability as well as sex-specific differences supporting an epigenetic link between early exposure to Pb and later-in-life health outcomes. Environ. Mol. Mutagen. 58:540-550, 2017. © 2017 Wiley Periodicals, Inc.

Heart rate-based window segmentation improves accuracy of classifying posttraumatic stress disorder using heart rate variability measures

Objective. Heart rate variability (HRV) characterizes changes in autonomic nervous system function and varies with posttraumatic stress disorder (PTSD). In this study we developed a classifier based on heart rate (HR) and HRV measures, and improved classifier performance using a novel HR-based window segmentation.Approach. Single-channel ECG data were collected from 23 subjects with current PTSD, and 25 control subjects with no history of PTSD over 24 h. RR intervals were derived from these data, cleaned, and used to calculate HR and HRV metrics. These metrics were used as features in a logistic regression classifier. Performance was assessed via repeated random sub-sampling validation. To reduce noise and activity-related effects, we calculated features from five non-overlapping ten-minute quiescent segments of RR intervals defined by lowest HR, as well as random ten-minute segments as a control.Main Results. Using a combination of the four most predictive features derived from quiescent segments we achieved a median area under the receiver operating curve (AUC) of 0.86 on out-of-sample test set data. This was significantly higher than the AUC using 24 h of data (0.72) or random segments (0.67).Significance. These results demonstrate our segmentation approach improves the classification of PTSD from HR and HRV measures, and suggest the potential for tracking PTSD illness severity via objective physiological monitoring. Future studies should prospectively evaluate if classifier output changes significantly with worsening or effective treatment of PTSD.

Planets and stellar activity: hide and seek in the CoRoT-7 system★

Since the discovery of the transiting super-Earth CoRoT-7b, several investigations have yielded different results for the number and masses of planets present in the system, mainly owing to the star's high level of activity. We re-observed CoRoT-7 in January 2012 with both HARPS and CoRoT, so that we now have the benefit of simultaneous radial-velocity and photometric data. This allows us to use the off-transit variations in the star's light curve to estimate the radial-velocity variations induced by the suppression of convective blueshift and the flux blocked by starspots. To account for activity-related effects in the radial-velocities which do not have a photometric signature, we also include an additional activity term in the radial-velocity model, which we treat as a Gaussian process with the same covariance properties (and hence the same frequency structure) as the light curve. Our model was incorporated into a Monte Carlo Markov Chain in order to make a precise determination of the orbits of CoRoT-7b and CoRoT-7c. We measure the masses of planets b and c to be 4.73 +/- 0.95 Mearth and 13.56 +/- 1.08 Mearth, respectively. The density of CoRoT-7b is (6.61 +/- 1.72)(Rp/1.58 Rearth)^(-3) g.cm^(-3), which is compatible with a rocky composition. We search for evidence of an additional planet d, identified by previous authors with a period close to 9 days. We are not able to confirm the existence of a planet with this orbital period, which is close to the second harmonic of the stellar rotation at around 7.9 days. Using Bayesian model selection we find that a model with two planets plus activity-induced variations is most favoured.

A Predictive Model of Health Promotion Behavior in Obese School-Age Children

The purpose of this study was to propose and to test a predictive model that could explain and predict the health promotion behavior of obese school-age children in Korea. Participants for this study were 365 students from 13 elementary schools located in Jeonbuk Province, Korea. The data were analyzed using SPSS 15.0 program and Amos 7.0 program. The results verified the factors that influence health promotion behavior of the participants. Important direct factors were prior health-related behavior, perceived self-efficacy, and commitment to a plan of action and indirect factors were perceived barrier and activity-related effect. These factors explained 75.3% of variance in the participants' health promotion behavior. The proposed model was concise and extensive in predicting health promotion behavior of the participants. Findings may provide useful assistance in developing effective nursing interventions for maintaining and promoting health promotion behavior in obese school-age children.

How stellar activity affects the size estimates of extrasolar planets

Lightcurves have long been used to study stellar activity and have more recently become a major tool in the field of exoplanet research. We discuss the various ways in which stellar activity can influence transit lightcurves, and study the effects using the outstanding photometric data of the CoRoT-2 exoplanet system. We report a relation between the `global' lightcurve and the transit profiles which turn out to be shallower during high spot coverage on the stellar surface. Furthermore, our analysis reveals a color dependence of the transit lightcurve compatible with a wavelength-dependent limb darkening law as observed on the Sun. Taking into account activity-related effects, we re-determine the orbit inclination and planetary radius and find the planet to be approximately 3% larger than reported previously. Our findings also show that exoplanet research cannot generally ignore the effects of stellar activity.

Maintenance on a ketogenic diet: voluntary exercise, adiposity and neuroendocrine effects

IntroductionAdherence to low-carbohydrate, ketogenic diets has been associated with greater weight loss in the short-term than low-fat, calorie-restricted diets. However, consumption of ketogenic diets may result in decreased voluntary exercise and thus render long-term weight loss and maintenance of weight loss difficult.MethodsRats were maintained on either a non-ketogenic chow (CH) diet or a low-carbohydrate, ketogenic diet (KD) for 6 weeks. Half of each dietary group was sedentary, while the other half was given access to a running wheel. Running wheel activity (total distance and meters/minute), plasma leptin and insulin, adiposity, and hypothalamic mRNA for neuropeptide Y (NPY) and proopiomelanocortin (POMC) were measured to assess activity-related effects in animals maintained on KD.ResultsWith access to a running wheel, rats on KD engaged in similar levels of voluntary activity as CH rats and both dietary groups decreased caloric intake. Caloric intake increased over time such that it was significantly greater than sedentary controls after one month of access to the wheels, however body weight remained decreased. Sedentary rats maintained on KD had increased adiposity and plasma leptin levels and decreased hypothalamic POMC mRNA, as compared to sedentary CH rats. KD rats with access to a running wheel had similar levels of adiposity and plasma leptin levels as CH rats with access to running wheels, but significantly increased POMC mRNA in the arcuate.ConclusionWe demonstrate that maintenance on KD does not inhibit voluntary activity in a running wheel. Furthermore, prevention of KD-related increased adiposity and plasma leptin, as measured in sedentary KD rats, significantly increases levels of the anorexigenic neuropeptide POMC mRNA.

Eclipsing binary stars as tests of stellar evolutionary models and stellar ages

AbstractEclipsing binary stars provide highly accurate measurements of the fundamental physical properties of stars. They therefore serve as stringent tests of the predictions of evolutionary models upon which most stellar age determinations are based. Models generally perform very well in predicting coeval ages for eclipsing binaries with main-sequence components more massive than ≈1.2 M⊙; relative ages are good to ~5% or better in this mass regime. Low-mass main-sequence stars (M &lt; 0.8 M⊙) reveal large discrepancies in the model predicted ages, primarily due to magnetic activity in the observed stars that appears to inhibit convection and likely causes the radii to be 10–20% larger than predicted. In mass-radius diagrams these stars thus appear 50–90% older or younger than they really are. Aside from these activity-related effects, low-mass pre–main-sequence stars at ages ~1 Myr can also show non-coevality of ~30% due to star formation effects, however these effects are largely erased after ~10 Myr.

Physical (in)activity and endothelium‐derived constricting factors: overlooked adaptations

The inner surrounding of arterial vessels, the endothelium, is optimally located to detect changes in blood characteristics or blood flow that may result from changes in physical activity or from diseases. In response to physical stimuli, the endothelium varies its release of circulating vasoactive substances and serves as a source of local and systemic endothelium-derived dilator and vasoconstrictor factors. Endothelial dysfunction is one of the earliest markers of vascular abnormalities observed in cardiovascular disease and ageing. Exercise training is an efficient therapeutic strategy to improve endothelial function. Traditionally, studies on endothelial dysfunction and physical (in)activity-related effects on vascular adaptations are primarily focused on vasodilator substances (i.e. nitric oxide). One may suggest that augmentation of vasoconstrictor pathways (such as endothelin-1 and angiotensin II) contributes to the endothelial dysfunction observed after physical inactivity. Moreover, these pathways may also explain the exercise-induced beneficial cardiovascular adaptations. This review summarizes the current knowledge on the effects of physical (in)activity on several endothelium-derived vasoconstrictor substances.

Brain activity affects dynamic but not static autoregulation

A close correlation between neuronal activity and cerebral blood flow was documented (activation-flow coupling). The matter of an activity-related effect on autoregulation remains elusive. We modulated cortical activity by GABAergic inhibition in 10 pre-anestesized rats and compared effects on activation-flow coupling and autoregulation. Contralateral forepaw stimulation was used to assess activation-flow coupling. Somatosensory potentials as well as local flow velocity responses were recorded with surface electrodes and laser-Doppler flowmetry. Performing intermittent carotid compression we calculated from the laser-Doppler data the transient hyperemic response ratio as a parameter of dynamic cerebral autoregulation. Recovery of cerebral perfusion at the end of the compression phase served as an index of static autoregulation. Tests were performed at baseline and after four successive doses of midazolam (0.5 mg/kg), applied at 30 min intervals. Reversibility of the changes was evaluated by application of flumazenil (0.2 mg/kg). Resting flow velocity levels (162 ± 52 vs. 110 ± 62 U; p < 0.001), evoked potentials (N2-P1-amplitude; 13 ± 4 vs.6 ± 3 μV; p < 0.005), and resultant flow velocity responses (28 ± 12 vs. 4 ± 3%; p < 0.0001) decreased after the first dose of midazolam and then remained stable. A dose-dependent decrease was found for the transient hyperemic response ratio (28 ± 13 to 22 ± 14 to 15 ± 10 ( p < 0.05) to 9 ± 5% ( p < 0.025)) but not static autoregulation. After antagonism, all changes were reversible. Dynamic but not static cerebral autoregulation depends from neuronal activity and thus metabolic demand of neurons.

Bidirectional effects of benzodiazepine binding site ligands in the elevated plus-maze: differential antagonism by flumazenil and β-CCt

Recent research using genetically modified mice has pointed to the specific contribution of individual receptor subtypes to the various effects of benzodiazepines. The aim of this study was to examine the relative significance of α 1-containing GABA A receptors in the effects of modulators at the benzodiazepine site in the elevated plus-maze (EPM) under dim red light in rats. We tested the effects of the non-selective antagonist flumazenil (0–20.0 mg/kg), the preferential α 1-subunit selective antagonist β-carboline-3-carboxylate- t-butyl ester (β-CCt, 0–30.0 mg/kg), the non-selective agonist midazolam (0–2.0 mg/kg), the preferential α 1-subunit selective agonist zolpidem (0–2.0 mg/kg) and the non-selective inverse agonist methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM, 0–2.0 mg/kg). The influence of flumazenil (10.0 mg/kg) and β-CCt (30.0 mg/kg) on the effects of both kinds of agonists were also examined. The standard spatio-temporal parameters reflecting anxiety (percentage of open arm entries and time) and locomotion (closed and total arm entries) were analyzed. β-CCt did not affect behavior, while flumazenil at the highest dose (20.0 mg/kg) decreased indices of open arm activity and total arm entries. Midazolam at the dose of 1.0 mg/kg significantly increased the percentage of open arm time, whereas at 2.0 mg/kg both anxiety-related parameters were increased. In contrast to the open arm entries, the open arm time was independent of the decreased closed arm entries, observed at 2.0 mg/kg. Flumazenil abolished these effects, whereas β-CCt partially potentiated the anxiolytic actions of midazolam. Zolpidem significantly increased both open-arm indices at 1.0 mg/kg, but the effect was dependent on the decreased closed arm entries. The selectivity of the anxiolytic-like effects of zolpidem was further checked under brighter white illumination. In these settings, the influence on anxiety-related, but not activity-related parameters, was absent. All of the activity-related effects of midazolam and zolpidem were mainly counteracted by both antagonists. DMCM produced significant anxiogenic effects at 1.0 mg/kg (open arm time) and 2.0 mg/kg (both parameters). β-CCt (30.0 mg/kg) and flumazenil at higher dose (20.0 mg/kg) antagonized the effects of DMCM. The results indicate the anxiolytic effects of a non-selective benzodiazepine site agonist involve a predominant role of subunits other than α 1, whereas the behavioral indices of the anxiolytic-like properties of an α 1-selective ligand, if observed, depend on the experimental settings and the changes in locomotor activity, and hence were behaviorally non-specific. The present results generally correspond well to the behavioral findings with the genetically modified mice. On the other hand, the relative significance of the α 1-subunit in the anxiogenic effects of DMCM could not be clearly deduced.

Chapter 3 Activity-dependent regulation of neuronal plasticity and self repair

Plasticity is an essential characteristic of the brain: it is part of how the brain functions and is continuous while the brain interacts with the outer world. The state of activation and the level of activity of the entire organism affect the brain's plastic response. Brain plasticity has many substrates, ranging from synapses to neurites and entire cells. The production of new neurons is part of plasticity even in the adult and old brain, but under normal conditions neurogenesis only occurs in two privileged regions of the adult brain: hippocampus and olfactory system. At least in the hippocampus, physical activity stimulates neurogenesis by acting on the proliferation of neuronal stem cells. More specific functions such as learning may be able to recruit new neurons from the pool of cells with neurogenic potential. In a broader context neuronal stem cells can likely be found throughout the brain. Therefore, novel approaches to neuroregeneration will, when most effective, make use of the activity-related effects on neuronal stem cells in the adult brain to activate these stem cells in a targeted manner to enhance brain function.