Curcumin for Attention Deficit Hyperactivity Disorder: a Behavioral Preliminary Investigation

Background: Curcumin has protective actions in neuropsychiatric disorders. Its mechanism of action is associated with the restoration of catecholaminergic balance, reduction of oxidative/nitrosative stress, protection against inflammation, and neuroprotection. Objective: In a first approach, the study presents an empty review of the potential effect of curcumin on cognitive performance in attention deficit hyperactivity disorder (ADHD).Methods: On a second moment, seeing the scarcity of studies and knowing that ADHD is related to hyperactive and anxious behavior, 20 spontaneously hypertensive Wistar rats (SHR) were divided into groups that received water (1 mg/kg/day), curcumin (50 mg/kg/day), or methylphenidate (1 mg/kg/day) for 42 days. Behavioral tests to assess activity (Open Field test), anxiety and impulsivity (Elevated Plus Maze, and Social Interaction), and memory (Y Maze and Object Recognition Test) were performed. Results: Animals treated with curcumin showed less anxious and hyperactive behavior. Related to the memory, the results can be related to hyperactivity. Conclusion: Thus, the data suggest that the treatments used here can beneficially modulate the anxious and hyperactive behavior of SHR.

Evaluation of homeopathic medicine in rats subjected to a hypercaloric diet and stress

Introduction: The factors related to obesity are complex, involving biologic, environmental and neuropsychological mechanisms[1-3]. Among the factors which influence the gain of weight, we can consider the stressful factors. Aims: The aim of this experiment was to evaluate the influence of the commercial homeopathic product compound by Fucus vesiculosus 1cH, Thyroidinum 5cH and Calcarea carbonica 5cH (Besomed®) in the gain of weight in animals submitted to hypercaloric diet and stress. Materials and Methods 40 male freshly weaned Wistar rats, ingesting hypercaloric food, were divided into 4 groups, being two groups submitted to stress by standstill, being one group treated and the other one for control (vehicle) and two more groups without stress being one treated and the other one for control. All were given the drink water ad libidum, in blind, for 2 months. The general activity was evaluated by the Open Field method in 2 steps, one after stress and one after 1 month of treatment. The weekly gain of weight was measured during the whole period of treatment. The data were analyzed by the ANOVA method of two ways followed by the Bonferroni test[4], being p≤0,05. Results: The treatment with Besomed® was effective in reducing only the gain of weight in the animals submitted to stress (p≤0,05); the evaluation of general activity in the Open Field showed increase in the time of freezing of these same animals after receiving the stressful stimulus. Discussion: The medicine is used as auxiliary in obesity treatment, and has the same both endogenous highdiluted molecules as the medicine used by similarity, which is the case of Calcarea carbonica, which, among others is indicated for obesity and hyperlipidemia[5], being observed in this study that the homeopathic complex group gained less weight than the other groups. Stress is capable of disturbing the physiological and psychological homeostasia of an individual, and when the stress is caused by standstill, it may induce behavior of the anxious type. There are also studies relating anxiety and feeding behavior in chronically stressed[6] individuals, showing that consuming a hypercaloric diet induces an anxious behavior[7] in male rats. In this study was not observed any change in the motor activity of animals which passed stress, however the time of freezing of the animals which took Besomed® was the lowest (p≤0,05) after stress, if compared to the control groups, demonstrating the absence of an anxious behavior. Conclusion: The medicine evaluated was effective in reducing weight and in inducing an adaptive behavior only in the stressed animals, reducing the evaluated parameters to the same levels observed in the control group.

Assessing and Treating Anxiety in Individuals with Autism

Anxiety is a cluster of responses that can involve both operant and respondent behavior, which can be both public and/or private in nature, and occurs when an upcoming aversive stimulus is signaled. Despite the reported high comorbidity of autism and anxiety, there has been very limited research on how to directly assess and treat anxiety, especially with individuals who have limited communication skills. In Study 1, anxiety was assessed in five individuals with autism, ranging in age from 10 to 19 years old. Anxiety was assessed by measuring behavior during (1) a baseline (with no putative anxiety-provoking stimuli present), (2) signals for an upcoming aversive event, and (3) exposure to that aversive event. Anxiety presented in several different ways, as both conditioned activation and suppression, and both with and without problem behavior during the aversive event. In Study 2, individualized treatments involving differential reinforcement of alternative responses and stimulus fading were used to successfully reduce anxious responding in all four participants who displayed anxiety. These studies demonstrated a potentially useful means of assessing anxiety in individuals with autism which may not only help to measure anxious behavior and identify anxiety-provoking events, but may also lead to effective treatment.

Evaluation of the ultradiluted medication MPD 30 CH in the offspring of mice mothers treated with methylphenidate during lactation.

Background: Methylphenidate (MPD) is a non-stimulating amphetamine that has being used for some time in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and, in adequate doses, it promotes the remission of symptoms and the improvement of important aspects, as social interaction and academic performance1, in patients with ADHD. Literature data indicates that MPD attenuates maternal behavior in mices2. According to this line of study, the work “Repeated methylphenidate administration during lactation reduces maternal behavior, induces maternal tolerance, and increases anxiety-like behavior in pups in adulthood”3 was carried out and confirmed that MPD administration during early lactation disrupts maternal behavior and causes anxiety in pups in adulthood. Would it be possible that ultradiluted and dynamized MPD change pups’ behavior? Objective: The aim of this study was to evaluate how the ultradiluted drug may or may not change the behavior of the animals at issue. Material and Methods: The medication was prepared according to the Brazilian Homeopathic Pharmacopeia, in the 30 CH dilution. The present study was approved by the Ethics Committee for Animal Experimentation of the Paulista University (No. 256/14 CEP / ICS / UNIP). Animals in this study were the same of the study above mentioned, and already published. Adult male mice were grouped among 13 animals of the experimental group (adults, offspring of mothers that received MPD during pregnancy) and 9 animals from the mother-control group, which did not take MPD during pregnancy. The 22 animals took ultradiluted MPD 30 CH medication in their drinking water ad libitum, for 20 days. In each water drinker, 5 drops of medication were added and stirred. Behavioral tests, such as the Open Field and the Light Dark Transition Test for mice, were performed. Data was analyzed statistically by the Student's T-Test to compare parametric data from two groups and the Mann-Whitney Test for nonparametric data, where p ≤ 0.05 is considered significant. Results and Discussion: In the Open Field Test, from the group of mothers medicated with methylphenidate during pregnancy, before the medication MPD 30 CH, animals showed a lower mobility and a greater immobility (p≤ 0.05) compared to the control-animals; after medication with the MPD 30 CH, animals exhibited an increase in mobility and a decrease in immobility, leading to no statistical difference between the medication group and the control group. In the Light Dark Transition Test for mice, experimental animals spent more time in the dark box and exhibited a decrease of the Rearing, presenting an anxious behavior; after the MPD medication, there were no more differences between experimental and control groups. Indiscriminate use of amphetamines has increased in recent years and this use, when not monitored, can cause serious adverse effects4. In this sense, ultradiluted medication can collaborate with the remission of possible undesirable effects. Conclusion: Initially, the MPD 30 CH changed the behavior shown by animals born from mothers that took methylphenidate during lactation and presented an anxious behavior as an unexpected effect. The mice that took the MPD 30 CH did not present the anxious behavior. Other experiments should be conducted to confirm the results of this study.

Anhedonic Type Behavior and Anxiety Profile of Wistar-UIS Rats Subjected to Chronic Social Isolation

Chronic Social Isolation (CSI) is a model of prolonged stress employed in a variety of studies to induce depression and anxious behavior in rats. The present study aims to evaluate the effect of CSI on male Wistar rats in terms of “anhedonic-type” behavior in the Sucrose Preference Test (SPT) and anxiogenic profile in the elevated-plus-maze (EPM) test, as well as evaluating the effect of resocialization upon sucrose consumption. A total of 24 adolescent male Wistar rats were evaluated. The animals were housed either together (communally) or socially isolated for 21 days, and then exposed for four consecutive days to the SPT test [water vs. a 32% sucrose solution (SS)]. Four days later, they were again subjected to the SPT test (32% vs. 0.7% SS), and then tested on the EPM apparatus 3 days later. Following the completion of the anxiogenic profile of the model, the animals were resocialized for 72 h and then re-tested once again using the SPT (32% vs. 0.7% SS). Twenty-four hours after this final consumption, the animals were euthanized to record the weight of their adrenal glands (AG). It was found that exposure to CSI produces anhedonic-type behavior and an anxiogenic profile in adolescent male rats, as evidenced in both the SPT and EPM tests, as well as in the animals’ physiological stress response. It was also demonstrated that resocialization does not reverse the anhedonic-type behavior, nor the physiological response to stress.

Pharmacological Inhibition of BTK reduces neuroinflammation and stress induced anxiety in vivo

Stress related disorders lead to serious psychiatric disabilities and are comorbid with anxiety and depression. Current therapies targeting several neurotransmitter systems are only able to mitigate symptoms partially. It is well recognized that stress and trauma related disorders lead to a prominent inflammatory response in humans, and in several animal models a robust neuroinflammatory response has been observed. However, the therapeutic potential of targeting specific components of the inflammatory response has not been adequately studied in this context. The current study investigated the NLRP3 - Caspase1-IL-1β pathway, which recent research has identified as a major contributor to exacerbated inflammatory response in several peripheral and central nervous system pathological conditions. Using two different models of stress, first - single prolonged restraint stress followed by brief underwater submersion and second - predator odor exposure in mice, we demonstrate heightened anxious behavior in mice one-week after stress. Females in both models display an exacerbated anxiety response than males within the stressed group. Consistent with this data stressed animals demonstrate upregulation of IL-1β, IL-6, Caspase1 activity and NLRP3 inflammasome activation in brain, with female animals showing a stronger neuroinflammatory phenotype. Pharmacological inhibition of NLRP3 inflammasome activation led to a rescue in terms of anxious behavior as well as attenuated neuroinflammatory response, both of which were significantly more prominent in female animals. Further, we observed induction of activated Bruton’s Tyrosine Kinase (BTK), an upstream positive regulator of NLRP3 inflammasome activation, in hippocampus and amygdala of stressed mice. Next, we conducted proof-of-concept pharmacological BTK inhibitor studies with Ibrutinib, a drug that is already FDA approved for use in certain types of lymphomas and leukemias, as well as a second inhibitor of BTK, LFM-A13. In both sets of experiments, we found inhibition of BTK significantly reduced the anxious behavior in stressed mice and attenuated the induction of NLRP3 inflammasome, Caspase 1 and IL1β. Our results suggest that BTK inhibition can be further investigated in context of human stress and trauma related disorders as a therapeutic strategy.

A influência do comportamento parental na adaptação da criança ao atendimento odontológico

The influence of parental anxiety on children produces aversive stimulus through negative personal reports, sometimes frightening, about traumatic dental treatments, fear produced by parents through verbal threats, in other words, the visit to the dentist cited as a threat, or as form of punishment. This assignment aims to understand, through bibliographical research and literature review, the influence of behavioral patterns of parents or guardians and it’s reflection on the accommodation and adaptation of the child to dental treatment. Thus, the specific objectives are: 1) to understand the influence of parental behavior on the infant patient in the face of dental care; 2) talk about the factors that can impact the levels of anxiety of the infant patient in the face of dental consultation or treatment. The literature review was made based on the search of scientific articles published in national and international journals, such as PubMed, Scielo, BVS, and bibliographic researches. The descriptors used as search parameters were anxiety, behavior, parental influence, pediatric dentistry and treatment. The articles were selected through the analysis of the summaries, which had as main subject the factors associated with dental anxiety and dental care. It’s expected to understand the external factors that cause fear and anxiety behaviors in the children as a patient, including the family's own anxious behavior and the dysfunctional patterns that affects the evolution of dental treatment, as well as the techniques and methods of reception and accommodation used by professionals pediatric dentistry, in order to enable the hypothesis for possible interventions.

Psychosocial Stress Hastens Disease Progression and Sudden Death in Mice with Arrhythmogenic Cardiomyopathy

Physiological stressors, such as exercise, can precipitate sudden cardiac death or heart failure progression in patients with arrhythmogenic cardiomyopathy (ACM). Yet, whether and to what extent a highly prevalent and more elusive environmental factor, such as psychosocial stress (PSS), can also increase ACM disease progression is unexplored. Here, we first quantified perceived stress levels in patients with ACM and found these levels correlated with the extent of arrhythmias and cardiac dysfunction. To determine whether the observed correlation is due to causation, we inflicted PSS-via the resident-intruder (RI) paradigm—upon Desmoglein-2 mutant mice, a vigorously used mammalian model of ACM. We found that ACM mice succumbed to abnormally high in-trial, PSS mortality. Conversely, no sudden deaths occurred in wildtype (WT) counterparts. Desmoglein-2 mice that survived RI challenge manifested markedly worse cardiac dysfunction and remodeling, namely apoptosis and fibrosis. Furthermore, WT and ACM mice displayed similar behavior at baseline, but Desmoglein-2 mice exhibited heightened anxiety following RI-induced PSS. This outcome correlated with the worsening of cardiac phenotypes. Our mouse model demonstrates that in ACM-like subjects, PSS is incisive enough to deteriorate cardiac structure and function per se, i.e., in the absence of any pre-existing anxious behavior. Hence, PSS may represent a previously underappreciated risk factor in ACM disease penetrance.