Involvement of catecholamines in the myocardium of rats submitted to experimental model of portal hypertension / Envolvimento das catecolaminas no miocárdio de ratos submetidos a modelo experimental de hipertensão portal

ABSTRACT Background: The role of autonomic nervous system in the development and maintenance of portal hypertension is not fully elucidated. It is known that the gene expression of norepinephrine in the superior mesenteric artery varies with time, and it may contribute for splanchnic vasodilation and its consequent hemodynamic repercussions. It is still not known exactly how the adrenergic expression behaves at the heart level in the initial stages of this process. Aim: To evaluate the immunohistochemical expression of the enzyme tyrosine hydroxylase (tyrosine 3-monooxygenase), involved in the synthesis of norepinephrine, in the myocardium of rats submitted to partial ligation of the portal vein. Methods: Twenty-four Wistar rats were divided into two groups: Sham Operated and Portal Hypertension. The partial ligation was performed in the Portal Hypertension group, and after 1/6/24 h and 3/5/14 days the animals were euthanized. Immunohistochemical analysis was performed to quantify the expression of the stained enzyme using the ImageJ program. Results: The Portal Hypertension group expressed percentages between 4.6-6% of the marked area, while the Sham Operated group varied between 4-5%. Although there was no statistical significance, the percentage stained in the Portal Hypertension group followed an increasing pattern in the first 6 h and a decreasing pattern after 24 h, which was not observed in the Sham Operated group. Conclusion: The expression of noradrenaline in rat myocardium during the first two weeks after partial ligation of the portal vein, with tyrosine hydroxylase as marker, did not show differences between groups over time.

RESUMO Racional: O papel do sistema nervoso autônomo na hipertensão portal não está completamente elucidado. Sabe-se que, nessa condição, a expressão gênica da norepinefrina na artéria mesentérica superior modifica-se com o tempo, podendo ser importante contribuinte para a vasodilatação esplâncnica e suas repercussões hemodinâmicas. Apesar dos estudos sobre as repercussões cardiovasculares na hipertensão portal, ainda não se sabe como a expressão adrenérgica se comporta a nível cardíaco nas etapas iniciais desse processo. Objetivo: Avaliar a expressão imunoistoquímica da enzima tirosina hidroxilase (tirosina 3-mono-oxigenase), relacionada à síntese da norepinefrina, no miocárdio de ratos submetidos à ligadura parcial da veia porta. Métodos: Foram utilizados 24 ratos, distribuídos em dois grupos: Sham Operated e Hipertensão Portal. A ligadura parcial da veia porta foi realizada apenas no grupo Hipertensão Portal e, após 1/6/24 h e 3/5/14 dias, os animais foram eutanasiados. Foi feita a análise imunoistoquímica para quantificar a expressão da enzima corada, utilizando o programa ImageJ. Resultados: No grupo Hipertensão Portal, o miocárdio expressou percentuais entre 4,6-6% de área marcada, enquanto que no grupo Sham Operated variou entre 4-5%, sem significância estatística. Apenas no grupo Hipertensão Portal, a porcentagem corada pela enzima seguiu padrão crescente nas primeiras 6 h e decrescente após 24 h. Conclusão: A expressão da noradrenalina no miocárdio de ratos durante as primeiras duas semanas após a ligadura parcial da veia porta, tendo como marcador a enzima tirosina hidroxilase, não apresentou diferenças entre grupos ao longo do tempo.

The neurobiology of infant maternal odor learning

Infant rats must learn to identify their mother’s diet-dependent odor. Once learned, maternal odor controls pups’ approach to the mother, their social behavior and nipple attachment. Here we present a review of the research from four different laboratories, which suggests that neural and behavioral responses to the natural maternal odor and neonatal learned odors are similar. Together, these data indicate that pups have a unique learning circuit relying on the olfactory bulb for neural plasticity and on the hyperfunctioning noradrenergic locus coeruleus flooding the olfactory bulb with norepinephrine to support the neural changes. Another important factor making this system unique is the inability of the amygdala to become incorporated into the infant learning circuit. Thus, infant rats appear to be primed in early life to learn odors that will evoke approach responses supporting attachment to the caregiver.

Neurobiologia dos transtornos do controle dos impulsos / The neurobiology of impulse control disorders

OBJETIVO: Revisar os artigos sobre substratos neurobiológicos dos transtornos do controle dos impulsos. O jogo patológico é o foco central desta revisão na medida em que a maioria dos estudos biológicos dos formalmente classificados como transtornos do controle dos impulsos examinou este transtorno. MÉTODO: Foi feita uma busca no banco de dados Medline de artigos publicados de 1966 até o presente para identificar aqueles relevantes para serem revisados neste artigo. DESFECHOS: Estudos pré-clínicos sugerem que a neuromodulação das monoaminas cerebrais está associada à tomada de decisões impulsivas e aos comportamentos de risco. Os estudos clínicos implicam diversos sistemas de neurotransmissores (serotoninérgico, dopaminérgico, adrenérgico e opióide) na fisiopatologia do jogo patológico e de outros transtornos do controle dos impulsos. Estudos de neuroimagem preliminares têm indicado o córtex pré-frontal ventromedial e o estriato ventral como atuantes na fisiopatologia do jogo patológico e de outros transtornos do controle dos impulsos. As contribuições genéticas para o jogo patológico parecem substanciais e os estudos iniciais têm relacionado esse transtorno a polimorfismos alélicos específicos, ainda que os achados de varredura genômica ainda tenham que ser publicados. CONCLUSÃO: Mesmo que tenham sido logrados avanços significativos em nossa compreensão sobre os transtornos do controle dos impulsos, mais pesquisas são necessárias para ampliar o conhecimento existente e traduzir esses achados em avanços clínicos.

OBJECTIVE: To review the neurobiological substrates of impulse control disorders. Pathological gambling is a main focus of the review in that most biological studies of the formal impulse control disorders have examined this disorder. METHOD: The medical database Medline from 1966 to present was searched to identify relevant articles that were subsequently reviewed to generate this manuscript. RESULTS: Preclinical studies suggest that differential brain monoamine neuromodulation is associated with impulsive decision-making and risk-taking behaviors. Clinical studies implicate multiple neurotransmitter systems (serotonergic, dopaminergic, adrenergic, and opioidergic) in the pathophysiology of pathological gambling and other impulse control disorders. Initial neuroimaging studies have implicated the ventromedial prefrontal cortex and ventral striatum in the pathophysiology of pathological gambling and other impulse control disorders. Genetic contributions to pathological gambling seem substantial and initial studies have implicated specific allelic polymorphisms, although genome-wide analyses have yet to be published. CONCLUSION: Although significant advances have been made in our understanding of the neurobiology of impulse control disorders, more research is needed to extend existing knowledge and translate these findings into clinical advances.

Biomarcadores tempranos en la enfermedad de Parkinson / Early biomarkers in Parkinson Disease

Luego del estudio de 43 pacientes con síndromes extrapiramidales (Parkinsonismos, Temblor esencial, Parálisis Supranuclear) mediante evaluaciones clínicas, por Resonancia Magnética y ecografía transcraneana se perfeccionó la metodología de evaluación incluyendo el estudio sistematizado de la región mesencefálica (SN;T) Unidades de Intensidad ROI; Grado 2: 85-105 y Grado 1: 105-115, detección de depósitos férricos mediante técnica de GRE y correlacionarlo con la evaluación del área de sección transversal por eco transcraneano y la determinación de grados de visualización ecográfica del mesencéfalo...Lo anterior nos ha permitido incluir en nuestras evaluaciones rutinarias cuestionarios para evaluar olfato y conducta alimentaria, relacionados con las alteraciones del núcleo accumbens como marcadores tempranos de Enfermedad de Parkinson. Asimismo nos ha permitido diferenciar entre los distintos cuadros con afectación del circuito extrapiramidal.

Role of norepinephrine in the regulation of rapid eye movement sleep.

Sleep and wakefulness are instinctive behaviours that are present across the animal species. Rapid eye movement (REM) sleep is a unique biological phenomenon expressed during sleep. It evolved about 300 million years ago and is noticed in the more evolved animal species. Although it has been objectively identified in its present characteristic form about half a century ago, the mechanics of how REM is generated, and what happens upon its loss are not known. Nevertheless, extensive research has shown that norepinephrine plays a crucial role in its regulation. The present knowledge that has been reviewed in this manuscript suggests that neurons in the brain stem are responsible for controlling this state and presence of excess norepinephrine in the brain does not allow its generation. Furthermore, REM sleep loss increases levels of norepinephrine in the brain that affects several factors including an increase in Na-K ATPase activity. It has been argued that such increased norepinephrine is ultimately responsible for REM sleep deprivation, associated disturbances in at least some of the physiological conditions leading to alteration in behavioural expression and settling into pathological conditions.

Important recent advances in cardiovascular adrenergic mechanisms

Five sub-areas were taken into consideration: Adrenoceptor subclassification: Presently, 10 different adrenoceptor subtypes have been characterized by pharmacological and molecular biology studies: Ó1A-, Ó1B-, Ó1D-, Ó2A/D, Ó2B-, Ó2C-, ß1-, ß2-, ß3- and ß4-adrenoceptors. Intracellular signaling: the adrenoceptors are members of a large superfamily of receptors linked to guanine-nucleotide proteins (G proteins), Ó1-adrenoceptors are coupled to Gq proteins and activate phospholipases, especially phospholipase Cß, Ó2-adrenoceptors are coupled to G1 proteins and inhibit adenylyl cyclase and in some tissues regulate potassium and calcium channels. Both ß1 and ß2-adrenoceptors are preferentially coupled to adenylyl cyclase through GS proteins and ß3-adrenoceptors appear to be coupled to K+ channel through a pertussis toxin-sensitive G1 protein. ß4-Adrenoceptors appear to be coupled positively to a cyclic AMP-dependent cascade and can undergo desensitization. Influence of maturation and ageing: From birth to old age important changes occur in animal models as in humans at the receptor level, neurotransmitter process and catecholamine disposition. In general terms, one can say that maturation is associated with a gradual increase of adrenergic influence, while ageing is associated with a reduction in the role of the adrenergic system on the regulation of physiologic processes. Cotransmission: ATP and the neuropeptide Y are cotransmitters with noradrenaline. While noradrenaline is the main transmitter in vascular tissues, ATP has functional relevance in some vessels and neuropeptide Y is mainly a modulator of noradrenaline release; it seems that it has an increased role under pathophysiological conditions like ischemia. Role of endothelium on noradrenaline release: Many substances produced by the endotelium or acting through the endothelium are able to influence noradrenaline release from sympathetic nerve varicosities of the blood vessel wall: some of them, like bradykinin and angiotensin II, exert a facilitatory, while others like NO and endothelin have an inhibitory effect on noradrenaline release evoked electrical nerve stimulation.

Exercício físico e memória / Physical exercise and memory

A memória é susceptível às influências endógena, hormonal e neuro-humoral especialmente logo após a aquisiçäo da informaçäo. A amígdala, o septo medial, o hipocampo e o córtex entorrinal estäo envolvidos nos processos de consolidaçäo, armazenamento e evocaçäo. A resposta ao problema dos mecanismos de armazenamento podem encontrar-se tanto pelo caminho da potenciaçäo delonga duraçäo como pelo das redes neurais, através de uma interaçäo complementar. A modulaçäo da memória enfoca a atençäo na análise das condiçöes sob as quais a consolidaçäo da memória pode ser alterada. Uma informaçäo adquirida em um determinado contexto neuro-humoral será melhor evocada se durante o processo de evocaçäo o contexto neuro-humoral for similar ao do momento da aquisiçäo, caracterizando a existência de uma periférica pós-treino de hormônios normalmente liberados por experiências emocionais e estresses, tais como: catecolaminas, ACTH, vasopressina, além do peptídio opióide B-endorfina. Os hormônios e opióides envolvidos na regulaçäo da memória também estäo envolvidos na regulaçäo, homeostática do exercício. Estudos têm demonstrado que a liberaçäo das catecolaminas, vasopressina, ACTH e B-endorfina é estimulada pelo exercício, fazendo-se uma relaçäo do efeito do exercício na regulaçäo da memória, especialmente exercícios intensos e os moderados de longa duraçäo

Does nitrous oxide produce an effect upon brain neurotransmitters namely dopamine, norepinephrine and serotonin and is it the answer to postoperative nausea and vomiting?

The effect of nitrous oxide [N2O] was studied on the changes of brain neurotransmitters [dopamine [DA], serotonin [5HT] and norepinephrine [NE]] in rats. Nitrous oxide was found to have no significant effect on the contents of NE, and 5HT, but decreases that of DA [mid- brain], thalamus-hypothalamus and medulla] after one hour. Decreased levels of DA indicated that, N2O increases dopaminergic neuronal activities in the mesocortical projections [midbrain, thalamus and hypothalamus] as well as the medullary network. The euphoric properties of nitrous oxide may be an indication of activation of mesocortical dopaminergic projection, while the increased incidence of emesis may indicate activation of medullary dopaminergic system. The observed plateau of the dopamine effect within the two hours of exposure could reflect the development of an acute tolerance to nitrous oxide. The effect of N2O on the liver function enzymes was studied as well as to investigate whether it has a hepatotoxic effect. Both enzymes tested, ALAT and ASAT, showed no significant difference from control

Monoamines and acetylcholine in primate cerebral cortex: what anatomy tells us about function

In primates, cholinergic and monoaminergic axons that innervate the cerebral cortex originate almost exclusively from subcortical nuclei in the brainstem and basal forebrain. These projections are thought to modulate cortical activity during arousal, attention and memory formation. Physiological and anatomical evaluations of these ascending projections suggest that they have overlapping but somewhat distinctive synaptic targets in the cortex. This review compares the anatomical organization of acetylcholine-, dopamine-, norepinephrine-, and serotonin-containing axon systems in the monkey and human cerebral cortex. Analysis of the distributions of axons, receptors, and synapses suggests that each system in likely to have a differential role in modulating cortical function.

La atención selectiva I: teorías, estructurales cerebrales, y mecanismos neuroquímicos implicados / Selective attention I: theories, brain structures and neurochemical mechamisms implied

Para que el sistema nevioso central (SNC) puede procesar la gran cantidad de información sensorial a la cual está expuesto constantemente, debe efectuarse una selección de la información. Los procesos cerebrales que hacen posible esta selección se conocen como anteción selectiva. En esta revisión describimos las distintas etapas por las que ha transcurrido el concepto de atensión selectiva. Inicialmente, este concepto fue ignorado durante algún tiempo. Este olvido se debió, en parte, a la influencia dominante del análisis experimental de la conducta. Esta situación cambió con la descripción, en 1949, de la reacción de alertamiento producida por la estimulación eléctrica de la formación reticular del tallo cerebral. Recientmente, con la llegada de técnicas que permiten evaluar el funcionamiento del sistema nervioso con una alta resolución temporal y espacial, el estudio de las funciones cerebrales, en general, y de los procesos cognoscitivos, en particular, ha cobrado un nuevo impulso. Con base en las teorías del procesamiento de información, se han propuesto varios modelos para explicar cómo se efectúa la selección de estímulos sensoriales. Las teorías del "filtro" proponen que las señales irrelevantes deben ser excluidas del análisis con el fin de atender los mensajes de interés. Estas teorías difieren en el nivel del SNC, en el que ocurre la selección de la información. En un caso se propone que la selección de información importante ocurre en los primero relevos de la vía sensorial. Otras teorías sugieren que durante el procesamiento de información se establecen diferntes tipos de asociaciones de acuerdo con una jerarquía específica. De esta manera, la selección se llevaría a cabo en diferentes niveles. Se han desarrollado varias líneas de pensamiento que buscan el sitio en el cual ocurre la selección de información. Hay defensores de las teorías localizacionistas, globalistas o antilocalizacionistas, mientras que otros proponen la existencia de una jerarquía funcional o de sistemas distribuidos. Esta última idea deriva del concepto de ensamble neuronal propuesto por Hebb, el cual fue incorporado en la definición de Mountcastle de los módulos de procesamiento de información. Empleando técnicas de imagenología en pacientes con lesiones localizadas o en modelos animales, ha sido posible determinar las regiones cerebrales que participan en los procesos de atención. Se ha propuesto que estas regiones se encuentran en distintos niveles del sistema nervioso central Äen el tallo cerebral, el diencéfalo y la corteza cerebral- y presentan entre sí una gran interconectividad, formando circuitos o ensambles neuronales específicos relacionados con la atención. Recientemente, Posner sugirió que las funciones cognoscitivas están constituidas por ensambles de operaciones elementales que ocurren en regiones cerebrales específicas. Con el fin de determinar los mecanismos neuroquímicos relacionados con la atención selectiva, se han investigado sistemas específicos de neurotransmisión. Se ha puesto particular énfasis en el papel de las catecolaminas, ya que se ha observado que las neuronas que poseen estos neurotransmisiones muestran variaciones en sus niveles de activación relacionados con los distintos niveles de alertamiento o con la aplicación de estímulos sensoriales significativos. Así, el locus coeruleus, un núcleo norodrenérgico con proyecciones amplias hacia la corteza cerebral, ha sido asociado con los cambios ocurridos en la relación señal/ruido, lo cual permite que se haga la selección de estímulos relevantes entre las muchas señales que se encuentran en el ambiente. Más aún, se ha establecido que hay una relación entre los sitemas catecolaminérgicos y las alteraciones que se observan generalmente en la clínica. Además, lesionados estos sistemas es posible inducir déficits de atención. En la segunda parte de la revisión describimos los correlatos electrofisiológicos de la atención selectiva. Analizaremos los estudios en los que se registran los poptenciales provocados, la actividad unitaria y la respuesta otoacústica, y nos referiremos a las alteraciones de la atención más frecuente en el ser humano: la hemi-inatención, las alteraciones del aprendizaje y las ausencias de origen epiléptico

Locus coeruleus: implicaciones para la psiquiatría / Locus coeruleus: implications for psychiatry

El papel del Locus coeruleus (LC) en los desórdenes psiquiátricos ha sido estudiado durante los últimos años empleando una variedad de métodos. Estudios han sugerido que este núcleo noradrenérgico (NA) central posee diversos efectos neurofisiológicos, neurofarmacológicos y conductuales que podrían ser parte del sustrato neurológico para las emociones normales. El LC es el más grande de los núcleos NA centrales, es el origen de más del 70 por ciento de la NA cerebral y constituye la fuente principal de la inervación de regiones cerebrales probablemente involucradas en conductas complejas. Este núcleo tiene implicaciones en la vigilancia como también en la orientación global de la conducta hacia estímulos ambientales imperativos. Recientes hallazgos respecto a la regulación visceral del LC proveen nuevos datos sobre la conducta y las funciones mentales, permitiendo una visión más integrada del rol de la NA en la función global del individuo. Esta revisión resume estos hallazgos y delinea algunas implicaciones para la psiquiatria

Inervaçäo autônoma do útero de mamíferos / Autonomic Innervation of the mammalian uterus

Apresenta-se uma revisäo sobre a inervaçäo autônoma do útero de mamíferos.

Effect of pirprofen on prostaglandins, norepinephrine, serotonin and dopamine content of rat brain

Estimation of prostaglandin E [2] [PGE [2]] level and of the chemical transmitters, serotonin [5-HT], norepinephrine [NE] and dopamine IDA content was performed in different parts of the brain of rats given pirprofen [36 mg/kg] by I.M. injection. The results showed a decrease in PGE [2] content in the thalamus and hypothalamus, and in dopamine content of the striatum with a significant increase in the nerotonin level of the mid brain, however, there was insignificant inecrease in the norepinephrine [NE] level of pons and medulla. 5-HT/NE and 5-HT/DA ratios were found to be raised by pirprofen. These data may help to explain the mechanism of activities of pirprofen as a non-steroidal anti-inflammatory drug

Role of opioid receptors in self-aggression in rats.

Self-aggression is a behavioural disorder in which an individual damages its own body parts by intense biting or scratching. Self aggression has been reported in human patients in Lesch-Nyhan syndrome and in cases of schizophrenia, depression, and congenital analgesia. In human patients as well as in experimental animals some kind of dysesthesia of the part of the body that is mutilated has been suggested. This study was conducted to find out the underlying pain mechanisms in self-aggressive behaviour arising out of stereotypy. The study was performed in 40 adult male rats. In all these animals, self-aggression was produced as part of amphetamine induced stereotyped behaviour. A predetermined scale was used for quantifying this behaviour. Reserpine and phenoxybenzamine pretreatment led to an increase in the incidence of self-aggression. Naloxone administration in reserpine pretreated animals led to a further significant increase in the incidence of self biting as compared to controls. From these studies it appears that self-aggressive behaviour may be associated with increased pain sensation.

Behavior effects of adrenaline and noradrenaline injected into the lateral ventricles of the pigeon (Columba Livia)

The behavioral effects of intravrnticular 1-micronl injections of adrenaline and noradrenaline (both in a concentration of 30 nmol/micronl) were wxamined in pigeons bearing cannule chronically implanted into the lateral ventricles. Injections of either catcholoamine evoked immediate and intense bouts of feeding behavior, followed by long-lasting incrases in sleep duration (50-90% higher than vehicle-treated subjects) in pigeons given free access to food during the observation period. Pigeons treated with adrenaline or vehicle only, and placed in a cage without the feeder set (food-deprived durngi the observation period), exhibited late increases in exploratory and preening behaviors, and less sleep than controls (vehicle-treated pigeons with free access to food). These data suggest that post-prandial sleep in this situation may represent a by-product of feeding-related processes evoked by both catecholamines

Resting tension and histopathology of intestinal smooth muscle of chagasic mice

La enfermedad de Chagas experimental se logró inoculando 45 tripomastigotes de T.cruzi cepa Tulahuen por animal (ratones Albinos Suizos de 3 meses de edad). Se estudió el efecto de NE y ACh sobre la tensión de reposo del músculo colónico desde los 2 días a los 180 días posteriores a la inoculación (p.i.). Desde los 2 a los 37 días p.i. el efecto de NE fue significativamente monor que el del grupo control. A partir de los 45 días p.i., no se observaron diferencias significativas con los valores normales. Durante la etapa aguda y hasta los 15 días p.i. las reacciones inflamatorias se caracterizaron por infiltrado de células mononucleares a nivel del plexo mioentérico y la pared intestinal. Fue frecuente la observación de parásitos en el tejido infectado; el efecto de ACh fue significativamente inferior en algunos de los gurpos de la etapa aguda, hecho que se mantuve constante en la etapa indeterminada (p < 0.001), persistiendo hasta los 5 meses p.i. A partir de los 165 días y hasta los 180 días p.i., la respuesta intestinal retornó una restitución "ad integrum" de los tejidos dañados. La respuesta farmacológica descripta en este modelo experimental sugiere que la Tripanosomiasis Americana produce alteraciones a nivel de los receptores muscarínicos únicamente en la etapa aguda e intermedia de la enfermedad de Chagas

Adrenergic urticaria: a first report from Thailand.

A 22-year-old, female patient came to see the allergists because of a 10-year history of chronic urticaria. Widespread pruritic, urticarial papules developed at times of stress and exercise, each papule being surrounded by a striking blanched vasoconstricted halo. The halo hives could be replicated with an intradermal injection of adrenaline. This is the first report of adrenergic urticaria from Thailand.

Efecto del agotamiento de la noradrenalina y la dopamina cerebrales de la rata sobre la actividad locomotriz espontánea y la estimulada por anfetamina / Effect of rat brain noradrenaline and dopamine depletion spontaneous and amphetamine induced stimulation

La destrucción de las fibras noradrenérgicas y dopaminérgicas por 6-hidroxidopamina, inyectada en la cisterna magna disminuye la actividad motora nocturna de las ratas en un 40% y bloquea en un 90%el efecto excitatorio de la anfetamina. El agotamiento selectivo de noradrenalina cerebral en más de un 70%, producido por inhibidores de la dopamina-beta-hidroxilasa (disulfiram, FLA-63), anula el efecto excitatorio de la anfetamina y además reduce la actividad motriz espontánea de las ratas, encontrándose en estos animales un contenido normal de dopamina en la corteza cerebral y el cuerpo extraído. En conclusión, estos resultados refuerzan la hipótesis que asigna a la noradrenalina el papel principal en el control de la actividad motriz de los roedores