Physical exercise-induced fatigue: the role of serotonergic and dopaminergic systems

Brain serotonin and dopamine are neurotransmitters related to fatigue, a feeling that leads to reduced intensity or interruption of physical exercises, thereby regulating performance. The present review aims to present advances on the understanding of fatigue, which has recently been proposed as a defense mechanism instead of a "physiological failure" in the context of prolonged (aerobic) exercises. We also present recent advances on the association between serotonin, dopamine and fatigue. Experiments with rodents, which allow direct manipulation of brain serotonin and dopamine during exercise, clearly indicate that increased serotoninergic activity reduces performance, while increased dopaminergic activity is associated with increased performance. Nevertheless, experiments with humans, particularly those involving nutritional supplementation or pharmacological manipulations, have yielded conflicting results on the relationship between serotonin, dopamine and fatigue. The only clear and reproducible effect observed in humans is increased performance in hot environments after treatment with inhibitors of dopamine reuptake. Because the serotonergic and dopaminergic systems interact with each other, the serotonin-to-dopamine ratio seems to be more relevant for determining fatigue than analyzing or manipulating only one of the two transmitters. Finally, physical training protocols induce neuroplasticity, thus modulating the action of these neurotransmitters in order to improve physical performance.

Valoración de los efectos fisiológicos y neuroquímicos de altas concentraciones de tetrahidrocannabinol en modelos biológicos / Assessment physiological and neurochemical effects of high concentrations of tetrahydrocannabinol in biological models

El objetivo de esta investigación fue evaluar los efectos fisiológicos y neuroquímicos en 60 ratones machos cepas Naval Medical Research Institute (NMRI) en edad adulto-joven con pesos promedios de 25,45 ± 3,05 g, sometidos durante seis semanas a dosis del principio psicoactivo de la marihuana el Δ-9-tetrahidrocannabinol en concentraciones entre 4 - 20%. Se realizaron tomas de sangre retroorbital para evaluar parámetros hematológicos y bioquímicos antes, durante y post experiencia. Se monitorearon medidas tales como: peso, ingesta de agua, alimentos, actividad locomotora horizontal y vertical, entre otros. Al final de la experiencia se realizo autopsia y toma de muestras de regiones cerebrales, para medir niveles de neurotransmisores aminoacidicos y dopamina. Estos resultados permiten concluir que altas concentraciones del principio psicoactivo de la marihuana hacen más dependiente al consumidor con los consecuentes daños fisiológicos y neurológicos. Esto lleva a que cada vez se necesite más droga para producir el mismo efecto.

The objective of this research was to evaluate the physiological and neurochemical effects in 60 (Naval Medical Research Institute) NMRI male mice strains in young adult - age average weight 25.45 ± 3.05 g, underwent six weeks at doses of the psychoactive ingredient in marijuana the Δ -9-tetrahydrocannabinol in concentrations between 4-20 %. Retroorbital blood shots were conducted to evaluate hematological and biochemical parameters before, during and post experience. Weight, water intake, food, horizontal and vertical locomotors activity include: measures such as monitored. At the end of the experience autopsy was conducted and sampling of brain regions to measure levels of amino acid neurotransmitters and dopamine. These results suggest that high concentrations of the psychoactive ingredient in marijuana consumers become more dependent with consequent physiological and neurological damage. This leads to more and more drugs is needed to produce the same effect.

Respiratory changes in Parkinson's disease may be unrelated to dopaminergic dysfunction / Alterações respiratórias na doença de Parkinson podem não ter relação com a disfunção dopaminérgica

OBJECTIVE: To investigate the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) in patients with Parkinson's disease (PD) during the on and off periods of levodopa and to compare with healthy controls. METHODS: Twenty-six patients were analyzed with Hoehn and Yahr scores (2-3) and 26 age and gender matched-controls. Statistical analysis was performed with Student's t-test for paired and independent samples. RESULTS: MIP and MEP values in patients were significantly lower than the values obtained in controls both for off and on stages -excepted for MIP in women (p=0.28). For patients with PD, the studied parameters did not differ between stages on and off, with the exception of MEP in women (p=0.00). CONCLUSIONS: Patients with PD have respiratory pressure lower than controls, even in early stages of the disease, and dopamine replacement has little impact over these respiratory pressures. These findings suggest that respiratory changes in PD may be unrelated to dopaminergic dysfunction.

OBJETIVO: Investigar as pressões inspiratórias máximas (PImáx) e as pressões expiratórias máximas (PEmáx) em pacientes com doença de Parkinson (DP) durante períodos on e off e comparar com controles MÉTODOS: Foram estudados 26 pacientes com scores de Hoehn e Yahr (2-3) e 26 indivíduos saudáveis pareados sexo e idade. A análise estatística foi realizada com o teste t de Student para amostras pareadas e para amostras independentes. RESULTADOS: Os valores de PImáx e PEmáx nos pacientes foram significativamente menores que os valores observados nos controles, tanto no período off como no período on -exceto PImáx nas mulheres (p=0,28). Nos pacientes com DP, os parâmetros estudados não diferiram entre os estágios off e on (exceto PEmáx nas mulheres-p=0,00). CONCLUSÕES: Pacientes com DP têm pressões respiratórias inferiores a controles mesmo em estágios iniciais da doença, e a reposição de dopamina tem pouco impacto sobre pressões respiratórias. Esses achados sugerem que as alterações respiratórias na DP podem não estar relacionadas às disfunções dopaminérgicas.

Actividad del sistema dopaminérgico renal en ratas con distinto contenido de sodio en la dieta / Activity of the renal dopaminergic system in rats

La dopamina (DA) renal modula la excreción de sodio y agua y la presión arterial por medio de receptores D1 (D1R) y D2 y es degradada por las enzimas monoamino-oxidasa (MAO) y catecol-O-metiltransferasa (COMT). Nuestro propósito es estudiar el patrón de excreción urinaria de DA (UDAV) y la actividad de MAO y COMT durante el consumo de dietas con distinto contenido de sodio.

Low frequency of bipolar disorder, dopamine dysregulation syndrome, and punding in Brazilian patients with Parkinson's disease / Baixa frequência de transtorno bipolar, síndrome de desregulação dopaminérgica e punding em pacientes brasileiros com doença de Parkinson

OBJECTIVE: To investigate the frequency of bipolar disorder, dopamine dysregulation syndrome and punding in Parkinson's disease patients from a Brazilian movement disorders clinic. METHOD: One hundred patients underwent a comprehensive psychiatric examination composed of MINI-plus and specific questionnaires to investigate dopamine dysregulation syndrome and punding. RESULTS: We identified, respectively, one and five Parkinson's disease patients with bipolar disorder type I and type II. All manic/hypomanic episodes occurred before Parkinson's disease onset. No patient was identified with dopamine dysregulation syndrome or punding. CONCLUSION: The frequency of manic/hypomanic episodes seems to decrease with Parkinson's disease onset, and local environmental factors (e.g. drug availability) may be responsible for the low frequency of dopamine dysregulation syndrome and punding in Brazilian Parkinson's disease patients.

OBJETIVO: Investigar a frequência de transtorno bipolar, síndrome de desregulação dopaminérgica e punding em pacientes com doença de Parkinson de uma clínica de movimentos anormais no Brasil. MÉTODO: Cem pacientes foram submetidos à avaliação psiquiátrica composta pelo MINI-Plus e questionários específicos para investigar síndrome de desregulação dopaminérgica e punding. RESULTADOS: Identificamos, respectivamente, um e cinco pacientes com transtorno bipolar tipo I e tipo II. Todos os episódios maníacos/hipomaníacos ocorreram antes do início da doença de Parkinson. Nenhum paciente foi identificado com síndrome de desregulação dopaminérgica ou punding. CONCLUSÃO: A frequência de episódios maníacos/ hipomaníacos parece declinar com o início da doença de Parkinson. Fatores ambientais locais (p.ex.: disponibilidade de drogas) podem ser responsáveis pela baixa frequência de síndrome de desregulação dopaminérgica e punding em pacientes brasileiros com doença de Parkinson.

Patterns of renal dopamine release to regulate diuresis and natriuresis during volume expansion: Role of renal monoamine-oxidase / Perfiles de secreción de dopamina renal en la expansión de volumen para regular diuresis y natriuresis: Rol de la monoaminoxidasa renal

Diuretic and natriuretic effects of renal dopamine (DA) are well established. However, in volume expansion the pattern of renal DA release into urine (U DA V) and the role of enzymes involved in DA synthesis/degradation have not yet been defined. The objective was to determine the pattern of U DA V during volume expansion and to characterize the involvement of monoamine-oxidase (MAO) and aromatic amino-acid decarboxylase (AADC) in this response. In this study male Wistar rats were expanded with NaCl 0.9% at a rate of 5% BWt per hour. At the beginning of expansion three groups received a single drug injection as follows: C (vehicle, Control), IMAO (MAO inhibitor Pargyline, 20 mg/kg BWt, i.v.) and BNZ (AADC inhibitor Benserazide, 25 mg/kg BWt, i.v.). Results revealed that in C rats U DA V (ng/30 min/100g BWt) increased in the first 30 min expansion from 11.5 ± 1.20 to 21.8 ± 3.10 (p < 0.05) and decreased thereafter. IMAO showed a similar pattern but significantly higher than C at 30 min expansion (32.5 ± 2.20, p < 0.05). IMAO greatly reduced MAO activity from 8.29 ± 0.35 to 1.1 ± 0.03 nmol/mg tissue/hour and significantly increased diuresis and natriuresis over controls. BNZ abolished the early U DA V peak to 3.2±0.72 (p < 0.01) and though, U DA V increased over C after 60 min expansion, natriuresis and diuresis were diminished by BNZ treatment. Results indicate that an increment in renal DA release into urine occurs early in expansion and in a peak-shaped way. In this response MAO plays a predominant role.

La dopamina (DA) intrarrenal ejerce efectos diuréticos y natriuréticos. Sin embargo, en los estado de expansión de volumen aún no está bien definido el patrón de liberación de dopamina renal hacia la orina y si cumplen un rol las enzimas involucradas en la síntesis o degradación de la amina. El objetivo del presente trabajo fue determinar el patrón de excreción urinaria de DA (U DA V) durante la expansión de volumen, caracterizando la participación de las enzimas monoaminooxidasa (MAO) y decarboxilasa de aminoácidos aromáticos (AADC) en esta respuesta. Para ello ratas Wistar macho fueron expandidas de volumen con NaCl 0.9% al 5% del peso corporal por hora durante dos horas y divididas en tres grupos, los que al comienzo de la expansión recibieron: C (vehículo, Control), IMAO (Pargilina, inhibidor de MAO, 20 mg/kg PC, i.v.) y BNZ (Benserazida, inhibidor de AADC, 25 mg/kg PC, i.v.). Se observó que en C la U DA V (ng/30min/100gPC) aumentó durante los primeros 30 minutos de expansión de 11.5 ± 1.20 a 21.8 ± 3.10 (p < 0.05), disminuyendo posteriormente. IMAO mostró un patrón de liberación similar pero significativamente mayor que C a los 30 min de expansión (32.5 ± 2.20, p < 0.05). En este grupo la actividad de MAO disminuyó de 8.29 ± 0.35 a 1.1 ± 0.03 nmol/mg tejido/hora y aumentaron la diuresis y natriuresis por sobre los controles. En BNZ, el pico de U DA V observado a los 30 min de la expansión disminuyó a 3.2 ± 0.72 (p < 0.01), aunque luego de 60 minutos fue mayor que en C. BNZ disminuyó tanto la diuresis como la natriuresis. Podemos concluir que al comienzo de la expansión de volumen se produce un pico de excreción de dopamina renal hacia la orina. La enzima MAO juega un rol fundamental en esta respuesta.

Lesion of the subthalamic nucleus reverses motor deficits but not death of nigrostriatal dopaminergic neurons in a rat 6-hydroxydopamine-lesion model of Parkinson's disease

The objective of the present study was to determine whether lesion of the subthalamic nucleus (STN) promoted by N-methyl-D-aspartate (NMDA) would rescue nigrostriatal dopaminergic neurons after unilateral 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). Initially, 16 mg 6-OHDA (6-OHDA group) or vehicle (artificial cerebrospinal fluid - aCSF; Sham group) was infused into the right MFB of adult male Wistar rats. Fifteen days after surgery, the 6-OHDA and SHAM groups were randomly subdivided and received ipsilateral injection of either 60 mM NMDA or aCSF in the right STN. Additionally, a control group was not submitted to stereotaxic surgery. Five groups of rats were studied: 6-OHDA/NMDA, 6-OHDA/Sham, Sham/NMDA, Sham/Sham, and Control. Fourteen days after injection of 6-OHDA, rats were submitted to the rotational test induced by apomorphine (0.1 mg/kg, ip) and to the open-field test. The same tests were performed again 14 days after NMDA-induced lesion of the STN. The STN lesion reduced the contralateral turns induced by apomorphine and blocked the progression of motor impairment in the open-field test in 6-OHDA-treated rats. However, lesion of the STN did not prevent the reduction of striatal concentrations of dopamine and metabolites or the number of nigrostriatal dopaminergic neurons after 6-OHDA lesion. Therefore, STN lesion is able to reverse motor deficits after severe 6-OHDA-induced lesion of the nigrostriatal pathway, but does not protect or rescue dopaminergic neurons in the substantia nigra pars compacta.

Amor y adicción: comparación de las características neurales y conductuales: [revisión] / Love and addiction: comparison of the neural and behavioral characteristics: [review]

El amor es una experiencia placentera que se encuentra presente en todas las culturas y que posee una compleja base neurobiológica que la sustenta. El sistema neural del placer es fundamental para dicha experiencia y al contrario de lo que normalmente se piensa, el amor está ligado más con el sistema motivacional que con emociones. Los núcleos y los neurotransmisores que sintetizan la experiencia del amor son los mismos que sustentan la adicción a las drogas como la cocaína, las anfetaminas o la morfina. Además los síntomas por abstinencia del consumo de drogas y los que se generan cuando se termina una relación de pareja son casi los mismos.

The love is a pleasant experience that is present in all the culture and that possesses a complex base neurobiological that sustains her. The neural system of the pleasure is fundamental for the above mentioned experience and unlike what normally this one thinks the love tied more with the system motivational that with emotions. The nucleuses and the neurotransmitters that they synthesize during the experience of the love are the same that sustain the addiction the drugs as the cocaine, the amphetamines and the morphine. In addition the symptom for abstinence of the consumption of drugs and those who are generated when a relation of pair finishes are almost the same one.

effects of ascorbic acid injection in to locus ceruleus and ventral tegmental area and PGi on morphine withdrawal signs in rats

Recent studies indicate that the glutamatergic and dopaminergic systems are involved in morphine withdrawal syndrome. Ascorbic acid [ascorbate] is an antioxidant vitamin released from glutamatergic neurons and modulates the synaptic action of dopamine and glutamate in the locus ceruleus, ventral tegmental area and PGi as well as behavior. To determine the effects of ascorbic acid injection into locus ceruleus, ventral tegmental area and PGi on morphine withdrawal signs in rats [MWS]. This was an experimental study in which a total of 80 male rats [250-300gr] divided into two were tested. The first group marked as control received 3% sucrose in tap water [n=10] and the second group [dependent group] received morphine and 3% sucrose in tap water [0.1, 0.2, 0.3, 0.4mg/ml each for 48h, and 0.4mg/ml for the remaining days up to day 21]. The latter was further divided into 7 subgroups as follows: [1] morphine group; [2, 3, and 4] sham operated groups which were surgically implanted with cannula at the locus ceruleus [LC], ventral tegmental area [VTA], and PGi; [5, 6, 7] morphine-ascorbic acid groups injected with AA [8 microg/microl] into LC, VTA, and PGi at day 21 and 5 min before naloxone administration. At the end of the training day, all groups received naloxone [2mg/kg I.P] and MWS was studied for 30 minute. Our results showed that the injection of ascorbate into LC and PGi caused a higher decrease in morphine withdrawal syndrome signs compared to VTA. Glutamatergic system is more effective than dopaminergic system in attenuation of MWS by acute injection of ascorbate

Interrelación entre el sistema dopaminérgico y las prostaglandinas / Interrelationship between the dopaminergic system and prostaglandins

En esta revisión se analiza el rol de la dopamina (DM) sobre la función renal y la relación de la DM con el sistema de las prostaglandinas (PGs), como la acetilcolinuria, bradiquinina y clonidina producen vasodilatación renal y natriuresis al ser infundidas y estos efectos son bloqueados o atenuados cuando la producción de prostaglandina es inhibida con drogas antinflamatorias no esteroides tales como la indometacina (IMT). Las PGs pueden ser una vía final común para el efecto vasodilatador de las sustancias mencionadas más arriba.Además, el antagonismoentre DM y hormona antidiurética se demuestra por la generación de diuresis acuosa máxima por la administración de DM en sujetos normales y perros anestesiados.El bloqueo alfa con fenoxibenzamina permite administrar altas dosis de DM con efectos alfa adrenérgicos. Finalmente se postula el posible uso de DM para tratar el síndrome de secreción inapropiada de hormona antidiuretica.

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.

Modelagem neurocomputacional do circuito tálamo-cortical: implicações para compreensão do transtorno de défi cit de atenção e hiperatividade / A neurocomputational model for the thalamocortical loop: towards a better understanding of attention deficit hyperactivity disorder

CONTEXTO: A desatenção no transtorno de déficit de atenção e hiperatividade (TDAH) é principalmente associada à hipoatividade dopaminérgica mesocortical. Contudo, variações dopaminérgicas mesotalâmicas também afetam o controle da atenção e, possivelmente, originam alterações atencionais no TDAH. OBJETIVO: Elaboração de um modelo neurocomputacional a partir do conhecimento do funcionamento bioquímico dos sistemas dopaminérgicos mesocortical e mesotalâmico, a fim de investigar a influência dos níveis de dopamina na via mesotalâmica sobre o circuito tálamo-cortical e suas implicações nos sintomas de desatenção do TDAH. MÉTODO: Através de um conjunto de equações modelamos propriedades fisiológicas de neurônios talâmicos. A seguir, simulamos computacionalmente o comportamento do circuito tálamo-cortical variando os níveis de dopamina nas vias mesotalâmica e mesocortical. RESULTADOS: Em relação à via mesotalâmica, a hipoatividade dopaminérgica dificulta o deslocamento do foco de atenção, e a hiperatividade dopaminérgica acarreta desfocalização atencional. Quando tais situações são acompanhadas de hipoatividade dopaminérgica mesocortical, surge uma incapacidade em perceber estímulos, devido à competição sem vencedores entre regiões talâmicas pouco ativadas. A desatenção no TDAH também se origina em desequilíbrios dopaminérgicos na via mesotalâmica, que levam à focalização excessiva ou à desfocalização da atenção. CONCLUSÃO: O nosso experimento in silico sugere que no TDAH a desatenção relaciona-se com alterações dopaminérgicas, que não se restringem à via mesocortical.

BAKGROUND: Inattention symptoms observed in patients with attention deficit hyperactivity disorder (ADHD) are mostly related to a hipoactivity in the mesocortical dopaminergic pathway. However, mesothalamic dopaminergic variations also affect the attentional control, and possibly lead to attention alterations in ADHD. PURPOSE: Elaborating a neurocomputational model from biochemical knowledge of mesocortical and mesotalamic dopamine systems, to investigate how different levels of mesothalamic dopamine influence the thalamocortical loop, leading to some attention deficits observed in ADHD. METHOD: First, we model physiological properties of thalamic neurons with a set of mathematical equations. Next, we simulate computationally the modeled thalamocortical loop under different levels of mesothalamic dopamine, and also the mesocortical dopaminergic decrease. RESULTS: Low levels of mesothalamic dopamine hinders the attentional shift and, high levels of such neuromodulator lead to distraction. When such alterations occur together with a decrease in the mesocortical dopamine level, the attention deficit turns into incapacity of perceiving environmental stimuli, due to a no winner competition between low activated thalamic areas. Inattention in ADHD also has its origins in dopaminergic disturbs throughout the mesothalamic pathway, which enhance a high focusing or do not allow the attention focus consolidation. CONCLUSION: In ADHD, the inattention is related to dopaminergic alterations that are not restricted to the mesocortical system.

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.

Resveratrol protects SH-SY5Y neuroblastoma cells from apoptosis induced by dopamine

Dopamine (DA) is an oxidant that may contribute to the degeneration of dopaminergic neurons. The present study demonstrates that DA-induced cytotoxicity in human-derived neurotypic cells, SH-SY5Y, is prevented by resveratrol, one of the major antioxidative constituents found in the skin of grapes. SH-SY5Y cells, a neuroblastoma cell line, treated with DA at 300 and 500 micrometer for 24 h underwent apoptotic death as determined by characteristic morphological features, including nuclear condensation, and loss of mitochondrial membrane potential (MMP). Flow cytometric analysis using Annexin V showed that DA can induce significant and severe apoptosis. Exposure to resveratrol (5 micrometer) for 1 h prior to the DA treatment attenuated DA-induced cytotoxicity, and rescued the loss of MMP. To investigate the apoptotic signaling pathways relevant to the restoration of DA-induced apoptosis by resveratrol, we carried out quantitative analysis of Bcl-2, caspase-3, and cleaved poly ADP-ribose polymerase (PARP) by immunoblot analysis. Resveratrol pretreatment led to a decrease in cleavage of PARP, an increase in the Bcl-2 protein, and activation of caspase-3. These results suggest that DA may be a potential oxidant of neuronal cells at biologically relevant concentrations. Resveratrol may protect SH-SY5Y cells against this cytotoxicity, reducing intracellular oxidative stress through canonical signal pathways of apoptosis and may be of biological importance in the prevention of a dopaminergic neurodegenerative disorder such as Parkinson disease.

Neurochemical estimations of some new quaternary phenacyl- bromopiperidinium compounds

Considering the fact that N-alkyl substituted quaternary ammonium salts of piperidinium bromide induce brain catecholamine and indoleamine metabolism, we thought it may he valuable to investigate the effects of three selected phenacyl derivatives [I, V and VIII] of piperidine on brain monoamines metabolism in mice [100mg/kg body weight] assuming that these derivatives might alter the brain indoleamine and catecholamine levels differently. Studies are carried out by using HPLC technique. It was found that compound VIII possessed greater neuroleptic activity as compared to compounds I and V

Neonatal handling and the expression of immunoreactivity to tyrosine hydroxylase in the hypothalamus of adult male rats

Neonatal handling has long-lasting effects on behavior and stress reactivity. The purpose of the present study was to investigate the effect of neonatal handling on the number of dopaminergic neurons in the hypothalamic nuclei of adult male rats as part of a series of studies that could explain the long-lasting effects of neonatal stimulation. Two groups of Wistar rats were studied: nonhandled (pups were left undisturbed, control) and handled (pups were handled for 1 min once a day during the first 10 days of life). At 75-80 days, the males were anesthetized and the brains were processed for immunohistochemistry. An anti-tyrosine hydroxylase antibody and the avidin-biotin-peroxidase method were used. Tyrosine hydroxylase-immunoreactive (TH-IR) neurons were counted bilaterally in the arcuate, paraventricular and periventricular nuclei of the hypothalamus in 30-æm sections at 120-æm intervals. Neonatal handling did not change the number of TH-IR neurons in the arcuate (1021 + or - 206, N = 6; 1020 + or - 150, N = 6; nonhandled and handled, respectively), paraventricular (584 + or - 85, N = 8; 682 + or - 62, N = 9) or periventricular (743 + or - 118, N = 7; 990 + or - 158, N = 7) nuclei of the hypothalamus. The absence of an effect on the number of dopaminergic cells in the hypothalamus indicates that the reduction in the amount of neurons induced by neonatal handling, as shown by other studies, is not a general phenomenon in the brain

Diagnóstico precoz de enfermedad de Parkinson: neurospect mediante trodat-1Tc99m, marcador del transportador dopamina / Early diagnosis of Parkinson's disease: neurospect by trodat-1Tc99m, dopamine transporter marker

ANTECEDENTES. Hemos comunicado recientemente que NeuroSPECT (NSP) del Transportador de Dopamina (DAT) es un método altamente sensible para el diagnóstico precoz de enfermedad de parkinson (27) OBJETIVOS. Evaluar la Sensibilidad de NSP de DAT en pacientes de hemiparkinsonismo, de novo y comparar los resultados contra laterales VS. Ipsilaterales al lado sintomático, así como la comparación con voluntarios sanos y evaluar así la sensibilidad para detectar alteraciones pre-sintomáticas y también las sintomáticas. MATERIAL Y MÉTODO. El presente estudio se refiere a 20 pacientes con hemiparkinsonismo de novo(HP) (UPDRS V =1) de 3.0 años promedio de evolución y 60.3 años de edad siendo 5/20 mujeres; el UPDRS III promedio era 14, Ocho HP izquierdo y 12 HP, derecho. Se comparan con 28 individuos normales, 21/28 mujeres con edad promedio 54 años. Se obtuvo imágenes tridimensionales mediante NST con 30 mCI del radiofármaco TRODAT-1 Tc99m cuatro horas después de la inyección intravenosa. RESULTADOS. En controles se observa máxima distribución del DAT en el caudado y putamen. Establecemos comparación con corteza occipital, que presenta mínima concentración no específica de DAT. En 20 pacientes con HP se observó disminución significativa de la concentración de DAT en comparación con la referencia cortical; esta anormalidad era bilateral con predominio en el núcleo contralateral al lado sintomático. La sensibilidad del Putamen para detectar Enfermedad de Parkinson es de 90 por ciento y la Especificidad es de 91 por ciento. En los controles normales se observó en 25 de los 28 pacientes un aumento marcado de la concentración de DAT en los núcleos caudado y putamen en comparación con la corteza de referencia. CONCLUSIÓN. La elevada sensibilidad de TRODAT 99m NeuroSPECT en pacientes con diagnóstico de enfermedad de Parkinson sintomático se manifiesta además por demostrar precozmente anormalidades en el estriado contralateral al lado sano aunque de menor magnitud, vale decir en estado presintomático