Hypericum perforatum chronic treatment affects cognitive parameters and brain neurotrophic factor levels

Objective: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats. Methods: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex. Results: Hypericum impaired the acquisition of short- and long-term aversive memory in male rats, evaluated in the inhibitory avoidance test. Female rats had no immediate memory acquisition and decreased short-term memory acquisition in the inhibitory avoidance test. Hypericum also decreased the recognition index of male rats in the object recognition test. Female rats did not recognize the new object in either the short-term or the long-term memory tasks. Hypericum decreased BDNF in the hippocampus of male and female rats. Hypericum also decreased NGF in the hippocampus of female rats. Conclusions: The long-term administration of hypericum appears to cause significant cognitive impairment in rats, possibly through a reduction in the levels of neurotrophic factors. This effect was more expressive in females than in males.

Grape juice increases the BDNF levels but not alter the S100B levels in hippocampus and frontal cortex from male Wistar Rats

ABSTRACT Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.

Alpha power oscillation in the frontal cortex under Bromazepam and Modafinil effects / Oscilações da potência alfa no córtex frontal sob influência do Bromazepam e Modafinil

ABSTRACTObjective Our aim was to investigate and compare the neuromodulatory effects of bromazepam (6 mg) and modafinil (200 mg) during a sensorimotor task analyzing the changes produced in the absolute alpha power.Method The sample was composed of 15 healthy individuals exposed to three experimental conditions: placebo, modafinil and bromazepam. EEG data were recorded before, during and after the execution of the task. A three-way ANOVA was applied, in order to compare the absolute alpha power among the factors: Group (control, bromazepam and modafinil) Condition (Pre and Post-drug ingestion) and Moment (pre and post-stimulus).Results Interaction was found between the group and condition factors for Fp1, F4 and F3. We observed a main effect of moment and condition for the Fp2, F8 and Fz electrodes.Conclusion We concluded that drugs may interfere in sensorimotor processes, such as in the performance of tasks carried out in an unpredictable scenario.

RESUMOObjetivo Investigar e comparar os efeitos neuromoduladores do bromazepam (6mg) e modafinil (200mg), durante a prática de uma tarefa sensoriomotora, analisando as modificações produzidas na potência absoluta de alfa.Método A amostra foi composta por 15 indivíduos saudáveis, expostos a três condições experimentais: Placebo, modafinil e bromazepam. Dados eletroencefalográficos foram registrados antes, durante e após a execução da tarefa motora. Um ANOVA three-way foi aplicado para comparar a potência absoluta de alfa nos fatores Grupo (controle, bromazepam e modafinil), Condição (Pré e Pós ingestão da droga) e Momento (Pré e Pós estimulo).Resultados Verificou-se interação entre os fatores grupo e condição para os eletrodos Fp1, F4 e F3. Observamos um efeito principal para momento e condição nos eletrodos Fp2, F8 e Fz.Conclusão Concluímos que as drogas, podem interferir em processos sensoriomotores, como no desempenho de tarefas executadas em um cenário imprevisível.

The effects of bromazepam over the central and frontal areas during a motor task: an EEG study / Os efeitos do bromazepam nas áreas corticais central e frontal durante execução de uma tarefa motora: um estudo de EEG

The present study investigates the influence of bromazepam while executing a motor task. Specifically, we intend to analyze the changes in alpha absolute power under two experimental conditions, bromazepam and placebo. We also included analyses of theta and beta frequencies. We collected electroencephalographic data before, during, and after motor task execution. We used a Two Way ANOVA to investigate the condition (PL × Br6 mg) and moment (pre and post) variables for the following electrodes: Fp1, Fp2, F7, F3, Fz, F4, F8, C3, CZ and C4. We found a main effect for condition on the electrodes FP1, F7, F3, Fz, F4, C3 and CZ, for alpha and beta bands. For beta band we also found a main effect for condition on the electrodes Fp2, F8 and C4; for theta band we identified a main effect for condition on C3, Cz and C4 electrodes. This finding suggests that the motor task did not have any influence on the electrocortical activity in alpha, and that the existing modifications were a consequence due merely to the drug use. Despite its anxiolytic and sedative action, bromazepam did not show any significant changes when the individuals executed a finger extension motor task.

O presente estudo investiga a influência do bromazepam durante a execução de uma tarefa motora. Especificamente, pretende-se analisar as mudanças na potência absoluta de alfa sob duas condições experimentais, bromazepam e placebo. Nós também incluímos as analises das frequências teta e beta. Foram coletados dados eletroencefalográficos antes, durante e depois da execução da tarefa motora. Usamos uma Anova de 2 fatores para investigar a condição (PL × Br6 mg) e variáveis no momento (pré e pós) para os seguintes eletrodos: Fp1, Fp2, F7, F3, Fz, F4, F8, C3, C4 e CZ. Encontramos um efeito principal para a condição e eletrodos FP1, F7, F3, Fz, F4, C3 e CZ para alfa e beta. Para beta também foi encontrado um efeito principal para condição nos eletrodos Fp2, F8 e C4; para theta nós identificamos um efeito principal para condition em C3, Cz e C4. Este achado sugere que a tarefa motora não tem qualquer influência sobre a atividade eletrocortical alfa e que as modificações existentes foram uma consequência devido o uso de drogas. Apesar de sua ação ansiolítica e sedativa, o bromazepam não apresentou mudança significativa quando os indivíduos executaram uma tarefa motora.

Aluminum and ethanol induce alterations in superoxide and peroxide handling capacity (SPHC) in frontal and temporal cortex.

Aluminum is an omnipresent neurotoxicant and has been associated with several neuropathological disorders. Cerebrum and cerebellum have been shown to face augmented oxidative stress when animals are exposed to aluminum and high doses of ethanol. To establish the link between oxidative stress and neurobehavioral alterations, the present study was conducted to determine the extent of oxidative stress in low levels of pro-oxidant (ethanol exposure) status of the functionally discrete regions of the cerebrum. Male Wistar rats were exposed to aluminum (10 mg/kg body wt) and ethanol (0.2-0.6 g/kg body wt) for 4 weeks. Spontaneous motor activity (SMA) and Rota-Rod performances (RRP) were recorded weekly during the period of exposure. At the end of 4th week, oxidative stress parameters were determined from the homogenized cerebral tissue. GSH-independent superoxide peroxide handling capacity (GI-SPHC) and GSH-dependent superoxide peroxide handling capacity (GD-SPHC) were determined for FC and TC upon exposure to ethanol in the absence and presence of aluminum exposure. Aluminum was found to augment the oxidative stress at higher doses (0.6 g Ethanol/kg body wt) of ethanol, particularly in FC. The SPHC of FC was also found to be compromised significantly in aluminum-ethanol co-exposed animals. It was concluded that even though the manifestation of oxidative stress was not observed as revealed by assaying the widely used oxidative stress biochemical markers (indices), aluminum and ethanol (low doses) exposure induced alterations in the handling capacity of oxidant imbalance that could be recognized by studying the SPHC of FC. Comparison of GD-SPHC and GI-SPHC offered a possible mechanism of compromised SPHC in FC. This observation is likely to offer insights into the mechanism of association between aluminium exposure and behavioral changes in neurodegenerative disorders towards therapeutic strategies for these disorders.

Restraint stress-induced central monoaminergic & oxidative changes in rats & their prevention by novel Ocimum sanctum compounds.

Background & objectives: Ocimum sanctum (OS) is known to possess various therapeutic properties. We have earlier isolated and characterized three OS compounds; Ocimarin, Ocimumoside A and Ocimumoside B. However, their role in modulating stress-induced central changes is unexplored. Thus, the present study was aimed to investigate the effect of these OS compounds on restraint stress (RS)-induced changes in the monoaminergic and antioxidant systems in the frontal cortex, striatum and hippocampus of rats. Methods: RS was produced by immobilizing (restraining) the Sprague Dawley rats for a period of 2.5 h inside cylindrical steel tubes. The monoamine levels and the in vivo antioxidant status in brain regions were evaluated by HPLC-EC and spectrophotometric assays, respectively. Results: RS significantly increased the dopamine levels in the frontal cortex and decreased in the striatum and hippocampus, and accompanied with selective increase of dopamine metabolites compared to the NS control group. The serotonin and its metabolite levels were significantly increased, while noradrenaline levels were decreased by RS in the three brain regions studied. The activities of superoxide dismutase and glutathione peroxidase in the frontal cortex and striatum were significantly increased by RS with decreased glutathione levels and increased lipid peroxidation. Pre-treatment with Ocimumoside A and B (40 mg/kg po) for a period of 3 days prevented the RS-induced changes with an efficacy similar to that of standard anti-stress (Panax quinquefolium; 100 mg/kg po) and antioxidant (Melatonin; 20 mg/kg ip) drugs, while, Ocimarin failed to modulate these changes. OS compounds per se had no effect on these parameters. Interpretation & conclusions: The present findings showed the anti-stress potential of Ocimumoside A and B in relation to their simultaneous modulatory effects on the central monoaminergic and antioxidant systems implicating their therapeutic importance in stress-related disorders. Further studies are required to understand the mechanism of action of these compounds.

Altered Brain Activation in Ventral Frontal-Striatal Regions Following a 16-week Pharmacotherapy in Unmedicated Obsessive-Compulsive Disorder

Recent studies have reported that cognitive inflexibility associated with impairments in a frontal-striatal circuit and parietal region is a core cognitive deficit of obsessive-compulsive disorder (OCD). However, few studies have examined progressive changes in these regions following clinical improvement in obsessive-compulsive symptoms. To determine if treatment changes the aberrant activation pattern associated with task switching in OCD, we examined the activation patterns in brain areas after treatment. The study was conducted on 10 unmedicated OCD patients and 20 matched controls using event-related functional magnetic resonance imaging. Treatment improved the clinical symptoms measured by the Yale-Brown Obsessive Compulsive Scale and behavioral flexibility indicated by the switching cost. At baseline, OCD showed significantly less activation in the dorsal and ventral frontal-striatal circuit and parietal regions under the task-switch minus task-repeat condition compared with controls. After treatment, the neural responses in the ventral frontal-striatal circuit in OCD were partially normalized, whereas the activation deficit in dorsal frontoparietal regions that mediate shifting attention or behavioral flexibility persisted. It is suggested that altered brain activation in ventral frontal-striatal regions in OCD patients is associated with their cognitive flexibility and changes in these regions may underlie the pathophysiology of OCD.

Embriopatía por isotretinoína: Un daño evitable / Isotretinoin embryophaty: Report of one case

Retinoic acid is a widely used drug in the treatment of cystic acné. It has teratogenic effects that depend on the gestational period in which it is used. We report a seven months of female whose mother was exposed to retinoic acid in both pregestational and gestational periods. She had a retardation of psychomotor development and a brain MRI showed frontal atrophy and a malformation of the posterior fossa. We discuss the mechanisms ofthe teratogenic effeets of retinoic acid.

Revisão: funcionamento executivo e uso de maconha / Review: executive functioning and cannabis use

OBJETIVO: A maconha é a droga ilícita mais consumida no mundo, porém ainda existem poucos estudos examinando eventuais prejuízos cognitivos relacionados ao seu uso. As manifestações clínicas associadas a esses déficits incluem síndrome amotivacional, prejuízo na flexibilidade cognitiva, desatenção, dificuldade de raciocínio abstrato e formação de conceitos, aspectos intimamente ligados às funções executivas, as quais potencialmente exercem um papel central na dependência de substâncias. O objetivo do estudo foi fazer uma revisão a respeito das implicações do uso da maconha no funcionamento executivo. MÉTODO: Esta revisão foi conduzida utilizando-se bases de dados eletrônicas (MedLine, Pubmed, SciELO and Lilacs). DISCUSSÃO: Em estudos de efeito agudo, doses maiores de tetrahidrocanabinol encontram-se associadas a maior prejuízo no desempenho de usuários leves em tarefas de controle inibitório e planejamento; porém, este efeito dose-resposta não ocorre em usuários crônicos. Embora haja controvérsias no que se refere a efeitos residuais da maconha, déficits persistentes parecem estar presentes após 28 dias de abstinência, ao menos em um subgrupo de usuários crônicos. CONCLUSÕES: Os estudos encontrados não tiveram como objetivo principal a avaliação das funções executivas. A seleção de testes padronizados, desenhos de estudos mais apropriados e o uso concomitante com técnicas de neuroimagem estrutural e funcional podem auxiliar na melhor compreensão das conseqüências deletérias do uso crônico da maconha no funcionamento executivo.

OBJECTIVE: Cannabis is the most used illicit drug worldwide, however only a few studies have examined cognitive deficits related to its use. Clinical manifestations associated with those deficits include amotivational syndrome, impairment in cognitive flexibility, inattention, deficits in abstract reasoning and concept formation, aspects intimately related to the executive functions, which potentially exert a central role in substance dependence. The objective was to make a review about consequences of cannabis use in executive functioning. METHOD: This review was carried out on reports drawn from MedLine, SciELO, and Lilacs. DISCUSSION: In studies investigating acute use effects, higher doses of tetrahydrocannabinol are associated to impairments in performance of nonsevere users in planning and control impulse tasks. However, chronic cannabis users do not show those impairments. Although demonstration of residual effects of cannabis in the executive functioning is controversial, persistent deficits seem to be present at least in a subgroup of chronic users after 28 days of abstinence. CONCLUSIONS: The neuropsychological studies found did not have as a main aim the evaluation of executive functioning. A criterial selection of standardized neuropsychological tests, more appropriate study designs as well as concomitant investigations with structural and functional neuroimaging techniques may improve the understanding of eventual neurotoxicity associated with cannabis use.

Haloperidol and clozapine differentially regulate signals pstream of glycogen synthase kinase 3 in the rat frontal cortex

Glycogen synthase kinase 3 (GSK3) was recently suggested to be a potential target of psychotropics used in psychiatric illnesses such as schizophrenia and bipolar disorder. Relevant studies have found that antipsychotic drugs regulate GSK3 activity via an increase in either inhibitory serine phosphorylation or amount of GSK3 after acute or subchronic treatment. Recent evidence shows that GSK3 is regulated by dopaminergic or serotonergic systems implicated in the pathophysiology and treatment mechanisms of schizophrenia and bipolar disorder. Therefore, antipsychotics may regulate GSK3 via antagonizing dopaminergic or serotonergic activity. However, the signaling pathway that is involved in GSK3 regulation by dopaminergic or serotonergic systems has not been well established. Haloperidol is a typical antipsychotic with potent dopamine D(2) receptor antagonism. Clozapine is an atypical antipsychotic with potent serotonin 5HT(2) receptor antagonism. We injected rats with haloperidol or clozapine and examined the phosphorylation and amount of GSK3alpha/beta and its well-known upstream regulators Akt and Dvl in the rat frontal cortex by Western blotting. Both haloperidol and clozapine induced Ser21/9 phosphorylation of GSK3GSK3alpha/beta. Haloperidol increased the Ser473 phosphorylation of Akt transiently, whereas clozapine maintained the increase for 1 h. Haloperidol did not affect the phosphorylation and amount of Dvl, whereas clozapine increased both phosphorylation and the amount of Dvl. Our results suggest that GSK3 activity may be regulated by both typical and atypical antipsychotics and that Akt or Dvl, depending on the D(2)- or 5HT(2)- receptor antagonism properties of typical and atypical antipsychotics, mediate the regulation differently.