Efeitos dos esteroides anabólicos androgênicos sobre funções cognitivas de ratos

The use and the demand for substances that enhance masculinity, strength and sexual power are not novel. Over the years, this search has assisted the research directions in this area, leading to the discovery of the primary male sex hormone testosterone in 1935. Since then, numerous testosterone analogue compounds were synthesized, which are generically called Anabolic Androgenic Steroids (AAS). The AAS were produced for therapeutic purposes, but an increase in the use of these compounds for other purposes occurred over time. Initially they were used mainly to improve performance in athletes. However, recent studies have shown that the use of AAS by non-athletes with aesthetical purposes have been increasing as well. The abuse of AAS with non-clinical purposes can promote a number of physiological alterations, such as heart, liver, respiratory and psychological problems such as changes in mood, levels of anxiety and aggression. Exposure to supraphysiological doses of AAS is associated with behavioral changes, however, little is known about the effects of AAS on cognitive functions. In this work, we aimed to mimic the AAS abuse in humans with intramuscular administration of a supraphysiological dose of testosterone propionate (TP) in rats. We investigated the effects of this treatment on different aspects of cognitive function, specifically learning, memory and anxiety. Adult male Wistar rats were tested in the spontaneous alternation, novel object recognition and plus-maze discriminative avoidance tasks. The control group received intramuscular injections of vegetable oil (vehicle), and the TP group received injections of TP (10 mg/kg, i.m.). The injections were administered for 40 days, with intervals of 48 hours (chronic treatment) or in a single injection (acute treatment). In addition to the behavioral assessments, we performed biochemical analyzes as indicators of the endocrine effects of the treatment. Our results show that chronic treatment with a supraphysiological dose of TP caused memory impairments in the novel object recognition and the discriminative avoidance tasks. The spatial working memory (evaluated by spontaneous alternation task) was not affected. Also, we did not observe changes in anxiety levels. Regarding the biochemical parameters, chronic treatment increased serum levels of glutamicpyruvic transaminase, an indicator of hepatic and pancreatic lesions (as those observed after chronic use of these substances in humans). On the other hand, acute treatment with PT did not promote significant changes in any of these parameters when compared to the control group. In summary, we conclude that chronic treatment with a supraphysiological dose of testosterone propionate produces memory deficits in novel object recognition and retrieval of the discriminative avoidance task in adult male rats

Efeitos de diferentes tipos estressores sobre a memória e aprendizagem de ratas

The exposure to stressors produces physiological changes of the organism in order to adapt the individual to the environment. Depending on the type, intensity and duration, stress can affect some cognitive functions, particularly processes of learning and memory. Several studies have also proposed that some level of anxiety would be necessary for memory formation. In this context, memories of previously aversive experiences may determine the manner and intensity with which are expressed fear responses, which explains the great interest in analyzing both anxiety and memory in animals. In addition, males and females demonstrate different reactions in relation to stressful stimuli, showing different levels of anxiety and differences in processing of the acquisition, retention and recall of information. Based on this information, the present study aimed to verify the effect of stress on learning, memory and anxiety behavioral parameters in rats exposed at different types of stressors of long duration (seven consecutive days): restraint (4h/day), overcrowding (18h/day) and social isolation (18h/day) in the different phases of the estrous cycle. Our results showed that the stress induced by restraint and social isolation did not cause changes in the acquisition process, but impaired the recall of memory in rats. Furthermore, it is suggested a protective effect of sex hormones on retrieval of aversive memory, since female rats in proestrus or estrus phase, characterized by high estrogen concentrations, showed no aversive memory deficits. Furthermore, despite the increased plasma levels of corticosterone observed in female rats subjected to restraint stress and social isolation, anxiety levels were unaltered, compared to those various stress conditions. Animal models based on psychological and social stress have been extensively discussed in the literature. Correlate behavioral responses, physiological and psychological have contributed in increasing the understanding of stress-induced psychophysiological disorders

O Tratamento com a fluoxetina (mas não com outros farmacos antidepressivo e ansioíiticos) reverte o déficit de memória aversiva causado por estresse agudo de contenção em camundongos

The physiologist H. Selye defined stress as the nonspecific response of the body to any factors that endanger homeostasis (balance of internal environment) of the individual. These factors, agents stressors, are able to activate the Hypothalamic-Pituitary-Adrenal (HPA) axis, thus resulting in the physiological responses to stress by the release of glucocorticoids that leads to psychophysiological changes, including effects on cognitive functions such as learning and memory. When this axis is acutely stimulated occurs a repertoire of behavioral and physiological changes can be adaptive to the individual. Notwithstanding, when the HPA axis is chronically stimulated, changes may favor the development of, such as anxiety disorders. Some drugs used in the clinic for the treatment of anxiety disorders these can exert effects on cognitive function, on the HPA axis and on the anxiety. In this context, the aim of our study was to investigate the effects of administration i.p. acute of diazepam (DZP, 2 mg/kg), buspirone (BUS, 3 mg/kg), mirtazapine (MIR, 10 mg/kg) and fluoxetine (FLU, 10 mg/kg) in male mice submitted to acute restraint stress, and evaluated using plus-maze discriminative avoidance task (PMDAT), which simultaneously evaluates parameters such as learning, memory and anxiety. Our results demonstrated that (1) the administration of DZP and BUS, but not FLU, promoted anxiolytic effects in animals; (2) administration mirtazapine caused sedative effect to animals; (3) in the training session, the animals treated with BUS, MIR and FLU learned the task, on the other hand DZP group showed impairment in learning; (4) in the test session, animals treated with DZP, BUS, and MIR showed deficits in relation to discrimination between the enclosed arms, aversive versus non-aversive arm, demonstrating an impairment in memory, however, animals treated with FLU showed no interference in the retrieval of this memory; (5) acute stress did not interfere in locomotor activity, anxiety, or learning on the learning task, but induced impairment in retrieval memory, and the group treated with FLU did not demonstrated this deficit of memory . These results suggest that acute administration of drugs with anxiolytic and antidepressant activity does not interfere with the learning process this aversive task, but impair its retrieval, as well as the acute restraint stress. However, the antidepressant fluoxetine was able to reverse memory deficits promoted by acute stress, which may suggest that modulation, even acutely serotonergic neurotransmission, by selectively inhibiting the reuptake of this neurotransmitter, interferes on the process of retrieval of an aversive memory

Sono e percepção visuoespacial em trabalhadores de uma empresa petroquímica submetidos a esquemas de trabalho em turnos alternantes

Shift work consists of an array of unusual work hours, such as evenings and weekends, and increasing workload, in order to meet the uninterrupted production, which leads to changes in the quality, duration and regularity of sleep. Research indicates that sleep alteration cause cognitive processes to become slower, unstable and prone to errors, leading to loss of cognitive functions such as visuospatial perception. In this sense, this research aimed to evaluate sleep quality and its relation to visuospatial perception in workers in alternating shifts. Participants were 21 panel operators in a petrochemical company, male, aged 19-53 years. All participants were subjected to schedules of alternating shifts (day and night) of 12 nonstop hours and data were collected from 10 workers who were assigned to the day shift and 11 workers assigned to the night shift. For the sleep evaluation were used the Sleep Diary, the Sleep Habits Questionnaire, the Chronotype Identification Questionnaire and the Pittsburgh Sleep Quality Index (PSQI). The visuospatial skills were assessed using the Rey Complex Figure Test and attention was assessed using a portable version of the Psychomotor Vigilance Task (PVT). The results showed that the general sample of workers obtained poor sleep quality on working days and good sleep quality during the work break. There was shortened sleep duration in the work week and appropriate duration in the work break. No losses were found in the workers visuospatiality, but the good quality of sleep during the work break was correlated to adequate visuospatial performance, for the day shift workers. The attention performance oscillated throughout the work hours, especially on the night shift. It is concluded that the alternating shifts work scheme can be detrimental to the sleep quality workers and a good sleep quality can contribute to a better visuospatial performance

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Investigação do funcionamento cognitivo de pacientes pediátricos diagnosticados com leucemia linfóide aguda - LLA

The present work investigated the cognitive operation of children diagnosed with acute lymphoblastic leukaemia (ALL), accompanied at pediatric oncologic institutions at the city of Natal/RN. Had participated in this study twenty children, of both sexes, between six and twelve years old, with the ALL diagnostic, who were in treatment (n=10) and out of treatment for at least one year (n=10) and were submitted exclusively to chemotherapy as CNS prophylaxis. The utilized protocol of neuropsychological evaluation covered the following cognitive abilities: intellective capability, attentional and memory systems, and executive functions. Data was analyzed through descriptive and inferential measures, with the support of the Mann-Whitney U Test and T-test, considering the influence of the variables sex, age at diagnostic and the past time since the beginning of the treatment over children s performance. The intellective capability evaluation showed low score to the out-of-treatment groups, female and children under five years old to the diagnostic. In concern of attentional systems, groups showed the expected performance. In a relevant way, in the evaluation of executive functions, were found reduced scores within all groups, especially inside the in-treatment group. Memory evaluation pointed to reduced performance in items concerning to learning evolution and spontaneous evocation after interference to the several groups. It can be concluded, reffer to the occurrence of transitory and permanent impact associated to the intrusion of chemotherapic components during the maturational course of the CNS. It s expected that the present investigation and the development of similar studies enable major comprehension about the mode, extension and repercussion of these damages subsidizing the development of strategies which may minimize them and provide better xxiii life quality to this clinical subgroup

Fenótipo neuropsicológico de adolescentes com síndrome de Down

This research aimed to contribute to the characterization of a neuropsychological phenotype of adolescents with Down Syndrome (DS). A multicases study of six adolescents (three males and three females, aged 13 to 14 years) diagnosed with DS and treated at two institutions in the city of Natal (Brazil), was conducted. Participants were assessed using the methodological approach developed by Luria, which is composed by four complementary stages. The first one aimed to investigate the qualitative impact of DS in school life and social development of the adolescents; dimensions of behavior and social-affective aspects of the members of the study were investigated. In the second stage participants performed a battery of neuropsychological tests in order to identify strengths and weaknesses in their cognitive functioning. The third stage was incorporated into the second in order to analyze the quality of the activity of the participants along the quantitative evaluation, highlighting strategies used, errors produced among other indicators. Lastly, the fourth stage refers to the intervention with the participants. Although this is not a specific objective of the study, it is argued that the outcome of this research will subsidize the practice of different professionals working with this clinical group. The results of the first stage emphasized the presence of difficulties in social relationships and in school life of observed adolescents. In turn, the second and third stages pointed out to the presence of difficulties in tasks involving logical and abstract thinking, as well as difficulties in expressive language. In relation to visual memory, we observed a better performance in activities of lower complexity, ie, with less interference of executive functioning, particularly in terms of the functions of planning and initiative. Finally, it was found motor and mental retardation, affecting significantly the performance related to different cognitive areas. The results highlighted here can be considered as subsidies for future interventions, suggesting the need for developping projects that take into account different aspects constituents of the human subject, involving not only the individual with developmental changes, as well as their families, teachers, schools and society in general

Avaliação das habilidades neurocognitivas em crianças e adolescentes sobreviventes da Leucemia Linfoide Aguda - LLA

The present study investigated the impact of the treatment modalities of Acute Lymphoblastic Leukemia on neurocognitive abilities of children and adolescents survivors, aged between 6 and 16 years of age, accompanied in pediatric oncology sectors of public health services in the cities of Campina Grande-PB and Natal-RN. The study included 52 children, 13 of these being children and adolescents diagnosed with leukemia and 39 healthy children matched in relation to the study group considering gender, age, school type and level of maternal education. Later the group of children with leukemia was subdivided into two subgroups depending on treatment modality which were submitted: Group 1A (only chemotherapy) and 1B (chemotherapy and radiotherapy). All participants were subjected to a battery of neuropsychological tests that investigated the following neurocognitive abilities: intellectual ability, memory system, attention, visuospatiality and visuoconstruction, processing speed and executive functions. Data were analyzed using descriptive and inferential measurements with the aid of the U test of Mann-Whitney and T test, considering the influence of the variables: sex, age at diagnosis, time since completion of treatment and level of schooling mothers, on the performance of children. Overall, it is concluded that the illness and the treatment of acute lymphoblastic leukemia significantly favors the emergence of cognitive deficits, particularly in terms of visuospatial skills, and executive skills visoconstrutivas. In turn, the treatment modality of radiotherapy is associated with the presence of more severe deficits, highlighting the significant impact on the speed of information processing. It is hoped that the results presented here will contribute to a better understanding of the nature and extent of neurocognitive effects arising ALL treatment

A relação entre transtorno da insônia e funções executivas em adultos

The insomnia disorder is defined as a difficulty initiating or maintaining sleep or waking up earlier than expected unable to return to sleep, followed by a feeling of nonrestorative and poor quality sleep, present for at least three months, with consequences on daytime functioning. Studies have shown that insomnia affects cognitive function, especially executive functions. However, researches that sought to investigate the relationship between primary insomnia and executive functioning were quite inconsistent from a methodological point of view, especially in regard to the variability of the used methods, the heterogeneity of diagnostic criteria for insomnia and the control of sleep altering drugs. In this sense, the present study aimed to investigate the relationship between insomnia and executive functions in adults. The participants were 29 people, from both genders, aged 20-55 years old. Participants were divided into three groups, one composed of 10 people with primary insomnia who used sleep medication (GIM), nine people with primary insomnia who did not use medication (GInM) and 10 healthy people who composed the control group (CG). The research was conducted in two stages. The first one involved a diagnostic evaluation for insomnia disorder through a clinical interview and the application of the following protocols: the Athens Insomnia Scale, the Insomnia Severity Index, Sleep Journal (for 14 days), Pittsburgh Sleep Quality Index (PSQI), the Stanford Sleepiness Test, depression and anxiety Beck inventories, and Lipp’s Iventory of stress symptoms for adults. After this stage, the evaluation of executive functions was performed by applying a battery of neuropsychological tests composed by the following tests: Wisconsin, Stoop Test, Colored trails Test, the Tower of London Test, Iowa Gambling Task (IGT) and WAIS III subtest digit span, which measured selective attention, inhibitory control, cognitive flexibility, planning, problem solving, decision making and working memory, respectively. The results showed that insomniacs (GIM and GInM) showed higher sleep latency, shorter sleep duration and lower sleep efficiency compared to the CG. In regard to the performance in executive functions, no statistically significant difference between groups was observed in the evaluated modalities. However, the data show evidence that, compared to GInM and GC, the performance of GIM was lower on tasks that required quick responses and changes in attention focus. On the other hand, GInM, when compared to GIM and GC, showed a better performance on tasks involving cognitive flexibility. Furthermore, impaired sleep measures were correlated with the worst performance of insomniacs in all components evaluated. In conclusion, people with the insomnia disorder showed a performance similar to healthy people’s in components of the executive functioning. Thus, one can infer that there is a relationship between primary insomnia and executive functions in adults.

Efeito agudo do exercício aeróbio vigoroso sobre as funções executivas em adolescentes

Executive functions are determinant cognitive processes for student success, since they execute and control complex cognitive activities such as reasoning, planning and solving problems. The development of the executive functions performances begin early at childhood going through the adolescence until adulthood, concomitant with the neuroanatomical, functional and blood perfusion changes over the brain. In this scenario, exercise has been considered an important environmental factor for neurodevelopment, as well as for the promotion of cognitive and brain health. However, there are no large scientific studies investigating the effects of a single vigorous aerobic exercise session on executive functions in adolescents. Objective: To verify the acute effect of vigorous aerobic exercise on executive functions in adolescents. Methods: A randomized controlled trial (RCT) with crossover design was used. 20 pubescent from both sexes/gender with age between 10 and 16 years were submitted to two sessions of 30min each: 1) The aerobic exercise session intensity was between 65 and 75% of heart rate reserve, in which 5min for warm-up, 20min at the target intensity and 5min of cool down; and 2) control session watching cartoons. The computerized Stroop test – Testinpacs and trail making test were used to evaluate the inhibitory control and cognitive flexibility assessment respectively, before and after both experimental and control sessions. The reaction time (RT) and number of errors (n) of Stroop test were recorded. The total time (TT) and the number of errors (n) of the trail making test were also recorded. Results: The control session’s RT did not present significant differences in the Stroop test. On the other hand, the exercise session’s RT decreased significantly (p<0.01) after the session. The number of errors made at the Stroop test had no significant differences in control and exercise sessions. The ΔTT of trail making test of exercise session was significantly (p<0.001) lower than the control session’s. Errors made in trail making test did not show significant differences between control and exercise sessions. Additionally, there was significant and positive association among the Stroop test ΔRT of exercise session with xiii chronological age (r= 0.635, p=0.001; r 2 = 0.404, p=0.003) and sexual maturation (rs= 0.580, p=0.007; r 2 = 0.408, p=0.002). Differently, there was no association among the control session ΔRT and chronological age (r= – 0.144, p=0.273; r 2 = 0.021, p=0.545) or sexual maturation (rs= –0.155, p=0.513; r 2 = 0.015, p=0.610). Conclusion: Vigorous aerobic exercise seems to improve acutely executive functions in adolescents. The effect of exercise on inhibitory control performance was associated to pubertal stage and chronological age. In other words, the benefits of exercise were more evident in early adolescence (↑ ΔRT) and its magnitude decreases along the growing up process.

Efeitos de um programa de treino cognitivo e das técnicas de higiene do sono para as funções executivas e para a qualidade de sono em idosos saudáveis

The aging process causes changes in the elderly’s sleep/awake standard impairing their cognitive abilities, particularly executive functioning, which already suffers loss by aging. The literature suggests that executive function and preserved sleep quality are key to maintaining good quality of life and independence of older people, requiring interventions to minimize the impact of losses incurred by the aging process. This study evaluated the effect of a cognitive training program and sleep hygiene techniques for executive functions and sleep quality in healthy older people. The participants were 41 healthy older adults, of both sexes, who were randomly divided into four groups: control group [GC], cognitive training group [GTC], sleep hygiene group [GHS] and training group + hygiene [GTH]. The research was developed in three stages: 1st - initial assessment of cognition and sleep; 2nd - specific intervention to each group; 3rd - post-intervention revaluation. The results showed that GTC had significant improvements in cognitive tasks flexibility, planning, verbal fluency and some aspects of episodic memory, besides gains in sleep quality and decrease on daytime hypersomnolence. The GHS improved sleep quality and daytime sleepiness as well and had significant improvements in insights capacity, planning, attention and in all evaluated aspects of episodic memory. The GTH had significant gains in cognitive flexibility, problem solving, verbal fluency, attention and episodic memory. The CG showed significant worsening in excessive daytime sleepiness in capacity planning. Thus, we conclude that cognitive training interventions and sleep hygiene strategies are useful in improving cognitive performance and quality of healthy elderly sleep.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.