Alpha-Synuclein Gene Alterations Modulate Tyrosine Hydroxylase in Human iPSC-Derived Neurons in a Parkinson's Disease Animal Model.

Parkinson's disease (PD) caused by SNCA gene triplication (3XSNCA) leads to early onset, rapid progression, and often dementia. Understanding the impact of 3XSNCA and its absence is crucial. This study investigates the differentiation of human induced pluripotent stem cell (hiPSC)-derived floor-plate progenitors into dopaminergic neurons. Three different genotypes were evaluated in this study: patient-derived hiPSCs with 3XSNCA, a gene-edited isogenic line with a frame-shift mutation on all SNCA alleles (SNCA 4KO), and a normal wild-type control. Our aim was to assess how the substantia nigra pars compacta (SNpc) microenvironment, damaged by 6-hydroxydopamine (6-OHDA), influences tyrosine hydroxylase-positive (Th+) neuron differentiation in these genetic variations. This study confirms successful in vitro differentiation into neuronal lineage in all cell lines. However, the SNCA 4KO line showed unusual LIM homeobox transcription factor 1 alpha (Lmx1a) extranuclear distribution. Crucially, both 3XSNCA and SNCA 4KO lines had reduced Th+ neuron expression, despite initial successful neuronal differentiation after two months post-transplantation. This indicates that while the SNpc environment supports early neuronal survival, SNCA gene alterations-either amplification or knock-out-negatively impact Th+ dopaminergic neuron maturation. These findings highlight SNCA's critical role in PD and underscore the value of hiPSC models in studying neurodegenerative diseases.

TNF-α Polymorphisms and Maternal Depression in a Mexican Mestizo Population.

BACKGROUND: Depressive disorders are common during pregnancy. There is compelling evidence that the inflammatory response system is important in the pathophysiology of depression. Higher concentrations of proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α) in depressed subjects have been described. Because several polymorphisms in the TNF-α promoter region are known to affect its gene expression, the aim of this study was determine whether TNF-α - 857C/T, -308G/A, and -238G/A polymorphisms confer susceptibility to depression during pregnancy in a Mexican mestizo population. METHODS: This case-control study involved 153 depressed pregnant women and 177 controls. Polymorphisms were genotyped using real-time PCR. Odds ratios (OR) and 95% confidence intervals adjusted by age, body mass index, number of pregnancies, months of pregnancy and number of abortions were used to estimate risk. RESULTS: The -857CT genotype was found to increase the risk for depression (OR= 1.73, 95% CI= 1.06-2.82). In contrast, the -238GA genotype reduced the risk (OR= 0.33, 95% CI= 0.14-0.72). The - 308G/A polymorphism was not associated with risk for depression. Finally, the C857-G308-A238 haplotype was associated with a decreased risk of depression (OR= 0.35, 95% CI= 0.15-0.82). CONCLUSION: Our results show for the first time an association between TNF-α -857C/T and -238G/A polymorphisms and prenatal depression in Mexican mestizo population.

The potential role of the novel hypothalamic neuropeptides nesfatin-1, phoenixin, spexin and kisspeptin in the pathogenesis of anxiety and anorexia nervosa.

Due to the dynamic development of molecular neurobiology and bioinformatic methods several novel brain neuropeptides have been identified and characterized in recent years. Contemporary techniques of selective molecular detection e.g. in situ Real-Time PCR, microdiffusion and some bioinformatics strategies that base on searching for single structural features common to diverse neuropeptides such as hidden Markov model (HMM) have been successfully introduced. A convincing majority of neuropeptides have unique properties as well as a broad spectrum of physiological activity in numerous neuronal pathways including the hypothalamus and limbic system. The newly discovered but uncharacterized regulatory factors nesfatin-1, phoenixin, spexin and kisspeptin have the potential to be unique modulators of stress responses and eating behaviour. Accumulating basic studies revelaed an intriguing role of these neuropeptides in the brain pathways involved in the pathogenesis of anxiety behaviour. Nesfatin-1, phoenixin, spexin and kisspeptin may also distinctly affect the energy homeostasis and modulate food intake not only at the level of hypothalamic centres. Moreover, in patients suffered from anxiety and anorexia nervosa a significant, sex-related changes in the plasma neuropeptide levels occurred. It should be therefore taken into account that the targeted pharmacomodulation of central peptidergic signaling may be potentially helpful in the future treatment of certain neuropsychiatric and metabolic disorders. This article reviews recent evidence dealing with the hypothetical role of these new factors in the anxiety-related circuits and pathophysiology of anorexia nervosa.

Role of N-Arachidonoyl-Serotonin (AA-5-HT) in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters Regulation.

The endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)], receptors (CB1 and CB2), enzymes such as [fatty acid amide hydrolase (FAHH) and monoacylglycerol lipase (MAGL)], as well as the anandamide membrane transporter. Although the role of this complex neurobiological system in the sleep-wake cycle modulation has been studied, the contribution of the blocker of FAAH/transient receptor potential cation channel subfamily V member 1 (TRPV1), N-arachidonoyl-serotonin (AA-5-HT) in sleep has not been investigated. Thus, in the present study, varying doses of AA-5-HT (5, 10, or 20 mg/Kg, i.p.) injected at the beginning of the lights-on period of rats, caused no statistical changes in sleep patterns. However, similar pharmacological treatment given to animals at the beginning of the dark period decreased wakefulness (W) and increased slow wave sleep (SWS) as well as rapid eye movement sleep (REMS). Power spectra analysis of states of vigilance showed that injection of AA-5-HT during the lights-off period diminished alpha spectrum across alertness in a dose-dependent fashion. In opposition, delta power spectra was enhanced as well as theta spectrum, during SWS and REMS, respectively. Moreover, the highest dose of AA-5-HT decreased wake-related contents of neurotransmitters such as dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT) whereas the levels of adenosine (AD) were enhanced. In addition, the sleep-inducing properties of AA-5-HT were confirmed since this compound blocked the increase in W caused by stimulants such as cannabidiol (CBD) or modafinil (MOD) during the lights-on period. Additionally, administration of AA-5-HT also prevented the enhancement in contents of DA, NE, EP, 5-HT and AD after CBD of MOD injection. Lastly, the role of AA-5-HT in sleep homeostasis was tested in animals that received either CBD or MOD after total sleep deprivation (TSD). The injection of CBD or MOD increased alertness during sleep rebound period after TSD. However, AA-5-HT blocked this effect by allowing animals to display an enhancement in sleep across sleep rebound period. Overall, our findings provide evidence that AA-5-HT is an important modulator of sleep, sleep homeostasis and neurotransmitter contents.

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis.

The endocannabinoid system comprises receptors (CB1 and CB2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents. However, no further evidence is available regarding the neurobiological role of the endocannabinoid system in the homeostatic control of sleep. Therefore, the aim of the current experiment was to test if SR141716A, URB597 or VDM-11 would modulate the sleep rebound after sleep deprivation. Thus, these compounds were systemically injected (5, 10, 20mg/kg; ip; separately each one) into rats after prolonged waking. We found that SR141716A and URB597 blocked in dose-dependent fashion the sleep rebound whereas animals treated with VDM-11 displayed sleep rebound during the recovery period. Complementary, injection after sleep deprivation of either SR141716A or URB597 enhanced dose-dependently the extracellular levels of dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT), as well as adenosine (AD) while VDM-11 caused a decline in contents of these molecules. These findings suggest that SR141716A or URB597 behave as a potent stimulants since they suppressed the sleep recovery period after prolonged waking. It can be concluded that elements of the endocannabinoid system, such as the CB1 cannabinoid receptor, FAAH and AMT, modulate the sleep homeostasis after prolonged waking.

Evidence that activation of nuclear peroxisome proliferator-activated receptor alpha (PPARα) modulates sleep homeostasis in rats.

The peroxisome proliferator-activated receptor alpha (PPARα) is a member of the nuclear receptor superfamily that has been suggested as a modulator of several physiological functions. The PPARα recognizes as an endogenous ligand the anorexic lipid mediator oleoylethanolamide (OEA) which displays wake-inducing properties. Despite that recent evidence indicates that activation of PPARα by synthetic agonists such as Wy14643 enhances waking as well as the extracellular contents of wake-related neurotransmitters, the role of PPARα in sleep recovery after prolonged waking has not been fully described. Thus, the aim of this study was to characterize if PPARα regulates sleep rebound after total sleep deprivation (TSD). We report that after 6h of TSD activation of PPARα by pharmacological systemic administration of OEA (10, 20 or 30mg/Kg, i.p.) promoted alertness by blocking the sleep rebound after TSD. Besides, wake-linked compounds such as dopamine, norepinephrine, serotonin, or adenosine collected from nucleus accumbens were enhanced after TSD in OEA-treated animals. These sleep and neurochemical results were mimicked after injection of PPARα agonist Wy14643 (10, 20, 30mg/Kg, i.p.). However, similar findings from the sham of vehicle groups were observed if PPARα antagonist MK-886 was administered to rats (10, 20, 30mg/Kg, i.p.). Our results strengthened the hypothesis that PPARα might modulate sleep and neurochemical homeostasis after sleep deprivation.

Sleep and neurochemical modulation by the nuclear peroxisome proliferator-activated receptor α (PPAR-α) in rat.

The peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear protein that plays an essential role in diverse neurobiological processes. However, the role of PPARα on the sleep modulation is unknown. Here, rats treated with an intrahypothalamic injection of Wy14643 (10µg/1µL; PPARα agonist) enhanced wakefulness and decreased slow wave sleep and rapid eye movement sleep whereas MK-886 (10µg/1µL; PPARα antagonist) promoted opposite effects. Moreover, Wy14643 increased dopamine, norepinephrine, serotonin, and adenosine contents collected from nucleus accumbens. The levels of these neurochemicals were diminished after MK-886 treatment. The current findings suggest that PPARα may participate in the sleep and neurochemical modulation.

Sleep deprivation and oxidative stress in animal models: a systematic review.

Because the function and mechanisms of sleep are partially clear, here we applied a meta-analysis to address the issue whether sleep function includes antioxidative properties in mice and rats. Given the expansion of the knowledge in the sleep field, it is indeed ambitious to describe all mammals, or other animals, in which sleep shows an antioxidant function. However, in this paper we reviewed the current understanding from basic studies in two species to drive the hypothesis that sleep is a dynamic-resting state with antioxidative properties. We performed a systematic review of articles cited in Medline, Scopus, and Web of Science until March 2015 using the following search terms: Sleep or sleep deprivation and oxidative stress, lipid peroxidation, glutathione, nitric oxide, catalase or superoxide dismutase. We found a total of 266 studies. After inclusion and exclusion criteria, 44 articles were included, which are presented and discussed in this study. The complex relationship between sleep duration and oxidative stress is discussed. Further studies should consider molecular and genetic approaches to determine whether disrupted sleep promotes oxidative stress.

Physical activity interventions in schools for improving lifestyle in European countries.

BACKGROUND: In the last decades, children's and adolescents' obesity and overweight have increased in European Countries. Unhealthy eating habits and sedentary lifestyle have been recognized to determine such an epidemic. Schools represent an ideal setting to modify harmful behaviors, and physical activity could be regarded as a potential way to avoid the metabolic risks related to obesity. Methods : A systematic review of the literature was carried out to summarize the evidence of school-based interventions aimed to promote, enhance and implement physical activity in European schools. Only randomized controlled trials were included, carried out in Europe from January 2000 to April 2014, universally delivered and targeting pupils aged between 3 and 18 years old. Results : Forty-seven studies were retrieved based either on multicomponent interventions or solely physical activity programs. Most aimed to prevent obesity and cardiovascular risks among youths. While few studies showed a decrease in BMI, positive results were achieved on other outcomes, such as metabolic parameters and physical fitness. Conclusion : Physical activity in schools should be regarded as a simple, non-expensive and enjoyable way to reach all the children and adolescents with adequate doses of moderate to vigorous physical activity.

Repetitive transcranial magnetic stimulation to treat substance use disorders and compulsive behavior.

Compulsions, like pathological gambling, binge-eating disorder, alcohol, tobacco or cocaine abuse and compulsive shopping have similar neurophysiological processing. This study aimed to examine the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving patient control over compulsive behavior. The rTMS modulatory role in cortical mesolimbic pathways possibly implies improvement of the inhibitory control system and compulsive consumption drive. Thus, craving reduction would be a component for control achievement. Within this context, 17 studies were found. Most studies applied rTMS over the left dorsolateral prefrontal cortex. Craving reduction was observed in 10 studies and was associated with improved control of compulsion in two of them. In one study reduction in consumption was found without reduction in craving. In addition, improvement in decision making was found in one study.

Diesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.

With the aim to develop beneficial tracers for cerebral tumors, we tested two novel 5-iodo-2'-deoxyuridine (IUdR) derivatives, diesterified at the deoxyribose residue. The substances were designed to enhance the uptake into brain tumor tissue and to prolong the availability in the organism. We synthesized carrier added 5-[125I]iodo-3',5'-di-O-acetyl-2'-deoxyuridine (Ac2[125I]IUdR), 5-[125I]iodo-3',5'-di-O-pivaloyl-2'-deoxyuridine (Piv2[125I]IUdR) and their respective precursor molecules for the first time. HPLC was used for purification and to determine the specific activities. The iodonucleoside tracer were tested for their stability against human thymidine phosphorylase. DNA integration of each tracer was determined in 2 glioma cell lines (Gl261, CRL2397) and in PC12 cells in vitro. In mice, we measured the relative biodistribution and the tracer uptake in grafted brain tumors. Ac2[125I]IUdR, Piv2[125I]IUdR and [125I]IUdR (control) were prepared with labeling yields of 31-47% and radiochemical purities of >99% (HPLC). Both diesterified iodonucleoside tracers showed a nearly 100% resistance against degradation by thymidine phosphorylase. Ac2[125I]IUdR and Piv2[125I]IUdR were specifically integrated into the DNA of all tested tumor cell lines but to a less extend than the control [125I]IUdR. In mice, 24 h after i.p. injection, brain radioactivity uptakes were in the following order Piv2[125I]IUdR>Ac2[125I]IUdR>[125I]IUdR. For Ac2[125I]IUdR we detected lower amounts of radioactivities in the thyroid and stomach, suggesting a higher stability toward deiodination. In mice bearing unilateral graft-induced brain tumors, the uptake ratios of tumor-bearing to healthy hemisphere were 51, 68 and 6 for [125I]IUdR, Ac2[125I]IUdR and Piv2[125I]IUdR, respectively. Esterifications of both deoxyribosyl hydroxyl groups of the tumor tracer IUdR lead to advantageous properties regarding uptake into brain tumor tissue and metabolic stability.

Orquestic regulation of neurotransmitters on reward-seeking behavior.

The ventral tegmental area is strongly associated with the reward system. Dopamine is released in areas such as the nucleus accumbens and prefrontal cortex as a result of rewarding experiences such as food, sex, and neutral stimuli that become associated with them. Electrical stimulation of the ventral tegmental area or its output pathways can itself serve as a potent reward. Different drugs that increase dopamine levels are intrinsically rewarding. Although the dopaminergic system represent the cornerstone of the reward system, other neurotransmitters such as endogenous opioids, glutamate, γ-Aminobutyric acid, acetylcholine, serotonin, adenosine, endocannabinoids, orexins, galanin and histamine all affect this mesolimbic dopaminergic system. Consequently, genetic variations of neurotransmission are thought influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. Here, we discuss current evidence on the orquestic regulation of different neurotranmitters on reward-seeking behavior and its potential effect on drug addiction.

Bupropion in the depression-related sexual dysfunction: a systematic review.

Depression is the most prevalent psychiatric disorder (16.6%) and is frequently associated with impairments in several areas. Sexual dysfunction (SD) is a prevalent problem with rates ranging from 40-45% in adult women and 20- 30% in adult men. A relationship between depression and sexual dysfunction has been shown in the literature although the mechanisms of this association are not yet clear. Many antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), list sexual dysfunction as a side effect. New drug alternatives with fewer side effects have been proposed, and bupropion is one of them. This study aims to review the literature on bupropion and its impact in sexual function on depressed subjects. Most of the studies have noted that bupropion is not only as effective as other antidepressants but has the advantage of a lower impact on sexual functioning. Some other studies have found that bupropion can even enhance sexual function in certain individuals. Bupropion is also effective, when combined with other antidepressants, in treating emergent sexual dysfunction. Bupropion may be an alternative treatment for depression that does not include the sexual side effects associated with most of the prescribed antidepressants available; however, additional research is required.

La especialización hemisférica y la regulación de la conducta motora desde la perspectiva de la neurociencia cognitiva / Hemispheric specialization and regulation of motor behavior on a perspective of cognitive neuroscience

Introducción Nuestra comprensión de la organización funcional del cerebro se debe a los avances en las técnicas de neuroimagen y a una intensa investigación clínica. Recientemente, la ciencia cognitiva (neurociencia cognitiva) en combinación con los avances tecnológicos han cambiado nuestra comprensión sobre la relación cerebro-conducta. Esta relación simbiótica ha permitido una mejor caracterización del sitio de la lesión en pacientes con trastornos cerebrales y de los patrones de activación en sujetos sanos. Objetivo En el presente artículo se discute la contribución del hemisferio izquierdo y la participación del hemisferio derecho en la regulación de la conducta motora; esto nos permitirá comprender mejor la lateralización de las funciones motoras. Desarrollo Los resultados apoyan la visión de un predominio del hemisferio izquierdo para el lenguaje y el control motor, y un predominio del hemisferio derecho para las funciones espaciales y la atención. Las áreas especializadas son probablemente predeterminadas y ciertas funciones están lateralizadas a uno u otro hemisferio, esto debido a la eficiente organización y procesamiento de la información en el cerebro. Conclusión En los estudios revisados, se observaron funciones específicas para cada hemisferio, lo que sugiere la existencia de una compleja organización que recluta a varias áreas del Sistema Nervioso para el adecuado desempeño de una tarea.

Introduction Our understanding of functional brain organization is due to advances in neuroimaging technologies and intensive clinical research. Recently, cognitive science (cognitive neuroscience), combined with advances in technology, have changed our understanding of brain-behavior relationship. This symbiotic relationship has allowed a better characterization of the lesion site in patients with brain disorders and patterns of activation in healthy subjects. Objective In this article we discuss the contribution of the left hemisphere and right hemisphere involvement in the regulation of motor behavior; this will allow us to better understand the lateralization of motor functions. Development The results support the view of a left hemisphere dominance for language and motor control, and a right hemisphere dominance for spatial functions and attention. Specialized areas are probably predetermined and certain functions are lateralized to one or other hemisphere due to the efficient organization and information processing in the brain. Conclusion In the studies reviewed, specific functions for each hemisphere were observed, suggesting the existence of a complex organization that recruits several areas of the Nervous System for proper task performance.

Extremely low-frequency electromagnetic fields activate the antioxidant pathway Nrf2 in a Huntington's disease-like rat model.

Transcranial magnetic stimulation (TMS) is a non-invasive technique used recently to treat different neuropsychiatric and neurodegenerative disorders. Despite its proven value, the mechanisms through which TMS exerts its beneficial action on neuronal function remain unclear. Recent studies have shown that its beneficial effects may be at least partly due to a neuroprotective effect on oxidative and cell damage. This study shows that TMS can modulate the Nrf2 transcriptor factor in a Huntington's disease-like rat model induced by 3-nitropropionic acid (3-NP). Western blot analysis demonstrated that 3-NP caused a reduction in Nrf2 in both cytoplasm and nucleus, while TMS applied to 3-NP-treated rats triggered an increase in cytoplasm and nucleus Nrf2 levels. It was therefore concluded that TMS modulates Nrf2 expression and translocation and that these mechanisms may partly explain the neuroprotective effect of TMS, as well as its antioxidant and cell protection capacity.

Clinical implication of Meissner`s corpuscles.

During the last decade skin biopsy has been confirmed as a tool to provide diagnostic information on some peripheral neuropathies. Most studies were focused on intraepithelial nerve fibers and few studies have investigated large myelinated fibers or whether corpuscles in human skin change quantitatively or qualitatively in pathologies of the peripheral or central nervous system. The main objective of this article is to provide a comprehensive review of Meissner's corpuscles including their distribution, density and age changes, development, molecular composition, cellular anatomy and physiology. We also describe their involvement in several pathologies and suggest including this dermal structure in the routine study of skin biopsies, looking for changes to be used as potential markers for several disorders. Finally the article draws the main aspects of how to study Meissner's corpuscles in skin biopsies and gives a view on future perspectives for implementing their use in clinical practice.

Motor neuron disease and acquired axonal neuropathy association in HIV infection: case report and update.

BACKGROUND: A possible viral etiology has been documented in the genesis of motor neuron disorders and acquired peripheral neuropathies, mainly due to the vulnerability of peripheral nerves and the anterior horn to certain viruses. In recent years, several reports show association of HIV infection with Amyotrophic Lateral Sclerosis - Syndrome, Motor Neuron Diseases and peripheral neuropathies. OBJECTIVE: To report a case of an association between Motor Neuron Disease and Acquired Axonal neuropathy in HIV infection, and describe the findings of neurological examination, cerebrospinal fluid, neuroimaging and electrophysiology. METHODS: The patient underwent neurological examination. General medical examinations were performed, including, specific neuromuscular tests, analysis of cerebrospinal fluid, muscle biopsy and imaging studies. RESULTS AND DISCUSSION: The initial clinical presentation of our case was marked by cramps and fasciculations with posterior distal paresis and atrophy in the left arm. We found electromyography tracings with deficits in the anterior horn of the spinal cord and peripheral nerves. Dysphagia and release of primitive reflexes were also identified. At the same time, the patient was informed to be HIV positive with high viral load. He received antiretroviral therapy, with load control but with no clinical remission. CONCLUSION: Motor Neuron disorders and peripheral neuropathy may occur in association with HIV infection. However, a causal relationship remains uncertain. It is noteworthy that the antiretroviral regimen may be implicated in some cases.

Cognitive mechanisms and motor control during a saccadic eye movement task: evidence from quantitative electroencephalography / Mecanismos cognitivos e controle motor durante uma tarefa de movimento sacádico dos olhos: evidências de eletroencefalografia quantitativa

The saccadic movement is an important behavioral measure used to investigate several cognitive processes, including attention and sensorimotor integration. The present study aimed at investigating changes in beta coherence over frontal, motor, occipital, and parietal cortices during the performance of two different conditions of a prosacadic paradigm. The conditions involved a different pattern of stimulus presentation: a fixed and random stimulus presentation. Twelve healthy volunteers (three male, mean age of 26.25 (SD=4.13) performed the task, while their brain activity pattern was recorded using quantitative electroencephalography. The results showed an interaction between factors condition and moment for the pair of electrode C3/C4. We observed a main effect for moment to CZ/C4, FZ/F3, and P3/PZ. We also found a main effect for condition to FZ/F4, P3/P4, and O1/O2. Our results demonstrated an important role of the inter-connection of the two hemispheres in visual search and movement preparation. The study demonstrates an automation of action and reduction of the focus of attention during the task. We also found that the inter-hemispheric beta coherence plays an important role in the differentiation of the two conditions, and that beta in the right frontal cortex is able to differentiate the conditions, demonstrating a greater involvement of procedural memory in fixed condition. Our results suggest a neuronal specialization in the execution of prosacadic paradigm involving motor task sequence.

O movimento sacádico é uma importante medida de comportamento usada para investigar vários processos cognitivos, incluindo atenção e integração sensório-motora. O presente estudo teve como objetivo investigar as mudanças na coerência em beta nos córtices frontal, motor, parietal e occipital durante a realização de duas condições diferentes de um paradigma do movimento sacádico. As condições envolveram um padrão diferente de apresentação do estímulo: a apresentação do estímulo fixo e do aleatório. Doze voluntários saudáveis ​​(três do sexo masculino, com idade média de 26,25; DP=4,13) realizaram a tarefa, enquanto o seu padrão de atividade cerebral era monitorado, usando eletroencefalografia quantitativa. Os resultados mostraram uma interação entre condição dos fatores e momento para o par de eletrodos C3/C4. Observou-se um efeito principal ao momento para CZ/C4, FZ/F3 e P3/PZ. Encontrou-se também um efeito principal à condição para FZ/F4, P3/P4 e O1/O2. Os resultados demonstram um importante papel da ligação interconexão entre os dois hemisférios, em busca visual e preparação do movimento. O estudo demonstra uma automatização da ação e uma redução do foco de atenção durante a tarefa. Identificou-se também que a coerência em beta entre regiões inter-hemisféricas desempenha um papel importante na diferenciação entre as duas condições. Ainda, beta no córtex frontal direito é capaz de diferenciar as condições, demonstrando-se um maior envolvimento da memória de procedimento em condição fixa. Sendo assim, os presentes resultados sugerem especialização neuronal na execução do paradigma prossacádico envolvendo sequência de tarefa motora.

Biodistribution and brain permeability of the extracellular domain of neuregulin-1-ß1.

Neuregulin-1 (NRG1) belongs to a large family of growth and differentiation factors with a key role in the development and maintenance of the brain. Genetic association of NRG1 within brain disorders such as Alzheimer's disease, schizophrenia and neuroprotective properties of certain NRG1 isoforms have led to a variety of studies in corresponding disease models. In the present work, we investigated NRG1 with regard to its peripheral and central biodistribution after systemic application. We first-time radiolabeled the entire biologically active extracellular domain of NRG1 isotype-ß1 (NRG1-ß1 ECD; aa 2-246) with iodine-125 and administered it peripherally to healthy adult C57Bl6 mice. Blood kinetics and relative organ distribution of (125)I-labeled NRG1-ß1 ECD were determined. The blood level of NRG1-ß1 ECD peaked within the first hour after intraperitoneal (i.p.) application. The brain-blood ratios of (125)I-labeled NRG1-ß1 ECD were time-dependently 150-370% higher compared to the brain impermeable control, (131)I-labeled bovine serum albumin. Autoradiographs of brain slices demonstrated that (125)I-labeled NRG1-ß1 ECD accumulated in several regions of the brain e.g. frontal cortex, striatum and ventral midbrain containing the substantia nigra. In addition we found histochemical and biochemical evidence that phosphorylation of the NRG1 prototype receptor ErbB4 was increased in these regions after systemic application of NRG1-ß1 ECD. Our data suggest that NRG1-ß1 ECD passes the blood-brain barrier and activates cerebral ErbB4 receptors.