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Search Results: 1 - 10 of 2364 matches for " Rosario Moratalla "
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Striatal Signaling in L-DOPA-Induced Dyskinesia: Common Mechanisms with Drug Abuse and Long Term Memory Involving D1 Dopamine Receptor Stimulation
Mario Gustavo Murer,Rosario Moratalla
Frontiers in Neuroanatomy , 2011, DOI: 10.3389/fnana.2011.00051
Abstract: Parkinson’s disease is a common neurodegenerative disorder caused by the degeneration of midbrain substantia nigra dopaminergic neurons that project to the striatum. Despite extensive investigation aimed at finding new therapeutic approaches, the dopamine precursor molecule, 3,4-dihydroxyphenyl-L-alanine (L-DOPA), remains the most effective and commonly used treatment. However, chronic treatment and disease progression lead to changes in the brain’s response to L-DOPA, resulting in decreased therapeutic effect and the appearance of dyskinesias. L-DOPA-induced dyskinesia (LID) interferes significantly with normal motor activity and persists unless L-DOPA dosages are reduced to below therapeutic levels. Thus, controlling LID is one of the major challenges in Parkinson’s disease therapy. LID is the result of intermittent stimulation of supersensitive D1 dopamine receptors located in the very severely denervated striatal neurons. Through increased coupling to Gαolf, resulting in greater stimulation of adenylyl-cyclase, D1 receptors phosphorylate DARPP-32, and other protein kinase A targets. Moreover, D1 receptor stimulation activates extracellular signal-regulated kinase and triggers a signaling pathway involving mammalian target for rapamycin and modifications of histones that results in changes in translation, chromatin modification, and gene transcription. In turn, sensitization of D1 receptor signaling causes a widespread increase in the metabolic response to D1 agonists and changes in the activity of basal ganglia neurons that correlate with the severity of LID. Importantly, different studies suggest that dyskinesias may share mechanisms with drug abuse and long term memory involving D1 receptor activation. Here we review evidence implicating D1 receptor signaling in the genesis of LID, analyze mechanisms that may translate enhanced D1 signaling into dyskinetic movements, and discuss the possibility that the mechanisms underlying LID are not unique to the Parkinson’s disease brain.
Methamphetamine and Parkinson's Disease
Noelia Granado,Sara Ares-Santos,Rosario Moratalla
Parkinson's Disease , 2013, DOI: 10.1155/2013/308052
Methamphetamine and Parkinson's Disease
Noelia Granado,Sara Ares-Santos,Rosario Moratalla
Parkinson's Disease , 2013, DOI: 10.1155/2013/308052
Abstract: Parkinson's disease (PD) is a neurodegenerative disorder predominantly affecting the elderly. The aetiology of the disease is not known, but age and environmental factors play an important role. Although more than a dozen gene mutations associated with familial forms of Parkinson's disease have been described, fewer than 10% of all cases can be explained by genetic abnormalities. The molecular basis of Parkinson's disease is the loss of dopamine in the basal ganglia (caudate/putamen) due to the degeneration of dopaminergic neurons in the substantia nigra, which leads to the motor impairment characteristic of the disease. Methamphetamine is the second most widely used illicit drug in the world. In rodents, methamphetamine exposure damages dopaminergic neurons in the substantia nigra, resulting in a significant loss of dopamine in the striatum. Biochemical and neuroimaging studies in human methamphetamine users have shown decreased levels of dopamine and dopamine transporter as well as prominent microglial activation in the striatum and other areas of the brain, changes similar to those observed in PD patients. Consistent with these similarities, recent epidemiological studies have shown that methamphetamine users are almost twice as likely as non-users to develop PD, despite the fact that methamphetamine abuse and PD have distinct symptomatic profiles. 1. Parkinson’s Disease Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting an estimated 7 to 10 million people worldwide. Incidence of the disease increases with age. PD usually affects people over the age of 50, but an estimated 4% of PD cases is diagnosed before the age of 50. Early in the course of the disease, the most obvious symptoms are movement-related. These include shaking, rigidity, slowness of movement, and difficulty with walking and gait. Later, cognitive and behavioral problems may arise, with dementia commonly occurring in the advanced stages of the disease. Other symptoms include sensory, sleep, and emotional problems. PD is caused by degeneration of midbrain dopaminergic neurons that project to the striatum. The loss of striatal dopamine is responsible for the major symptoms of the disease. Although a small proportion of cases can be attributed to known genetic factors, most cases of PD are idiopathic. While the aetiology of dopaminergic neuronal demise is elusive, a combination of genetic susceptibilities, age, and environmental factors seems to play a critical role [1]. Dopamine degeneration process in PD involves abnormal
Lack or Inhibition of Dopaminergic Stimulation Induces a Development Increase of Striatal Tyrosine Hydroxylase-Positive Interneurons
Carla Letizia Busceti, Domenico Bucci, Gemma Molinaro, Paola Di Pietro, Luca Zangrandi, Roberto Gradini, Rosario Moratalla, Giuseppe Battaglia, Valeria Bruno, Ferdinando Nicoletti, Francesco Fornai
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0044025
Abstract: We examined the role of endogenous dopamine (DA) in regulating the number of intrinsic tyrosine hydroxylase-positive (TH+) striatal neurons using mice at postnatal day (PND) 4 to 8, a period that corresponds to the developmental peak in the number of these neurons. We adopted the strategy of depleting endogenous DA by a 2-day treatment with α-methyl-p-tyrosine (αMpT, 150 mg/kg, i.p.). This treatment markedly increased the number of striatal TH+ neurons, assessed by stereological counting, and the increase was highly correlated to the extent of DA loss. Interestingly, TH+ neurons were found closer to the clusters of DA fibers after DA depletion, indicating that the concentration gradient of extracellular DA critically regulates the distribution of striatal TH+ neurons. A single i.p. injection of the D1 receptor antagonist, SCH23390 (0.1 mg/kg), the D2/D3 receptor antagonist, raclopride (0.1 mg/kg), or the D4 receptor antagonist, L-745,870 (5 mg/kg) in mice at PND4 also increased the number of TH+ neurons after 4 days. Treatment with the D1-like receptor agonist SKF38393 (10 mg/kg) or with the D2-like receptor agonist, quinpirole (1 mg/kg) did not change the number of TH+ neurons. At least the effects of SCH23390 were prevented by a combined treatment with SKF38393. Immunohistochemical analysis indicated that striatal TH+ neurons expressed D2 and D4 receptors, but not D1 receptors. Moreover, treatment with the α4β2 receptor antagonist dihydro-β-erythroidine (DHβE) (3.2 mg/kg) also increased the number of TH+ neurons. The evidence that DHβE mimicked the action of SCH23390 in increasing the number of TH+ neurons supports the hypothesis that activation of D1 receptors controls the number of striatal TH+ neurons by enhancing the release of acetylcholine. These data demonstrate for the first time that endogenous DA negatively regulates the number of striatal TH+ neurons by direct and indirect mechanisms mediated by multiple DA receptor subtypes.
Adenosine A2A Receptors in Striatal Glutamatergic Terminals and GABAergic Neurons Oppositely Modulate Psychostimulant Action and DARPP-32 Phosphorylation
Hai-Ying Shen, Paula M. Canas, Patricia Garcia-Sanz, Jing-Quan Lan, Detlev Boison, Rosario Moratalla, Rodrigo A. Cunha, Jiang-Fan Chen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080902
Abstract: Adenosine A2A receptors (A2AR) are located postsynaptically in striatopallidal GABAergic neurons, antagonizing dopamine D2 receptor functions, and are also located presynaptically at corticostriatal terminals, facilitating glutamate release. To address the hypothesis that these two A2AR populations differently control the action of psychostimulants, we characterized A2AR modulation of cocaine-induced effects at the level of DARPP-32 phosphorylation at Thr-34 and Thr-75, c-Fos expression, and psychomotor activity using two lines of cell-type selective A2AR knockout (KO) mice with selective A2AR deletion in GABAergic neurons (striatum-A2AR-KO mice), or with A2AR deletion in both striatal GABAergic neurons and projecting cortical glutamatergic neurons (forebrain-A2AR-KO mice). We demonstrated that striatum-A2AR KO mice lacked A2ARs exclusively in striatal GABAergic terminals whereas forebrain-A2AR KO mice lacked A2ARs in both striatal GABAergic and glutamatergic terminals leading to a blunted A2AR-mediated facilitation of synaptosomal glutamate release. The inactivation of A2ARs in GABAergic neurons reduced striatal DARPP-32 phosphorylation at Thr-34 and increased its phosphorylation at Thr-75. Conversely, the additional deletion of corticostriatal glutamatergic A2ARs produced opposite effects on DARPP-32 phosphorylation at Thr-34 and Thr-75. This distinct modulation of DARPP-32 phosphorylation was associated with opposite responses to cocaine-induced striatal c-Fos expression and psychomotor activity in striatum-A2AR KO (enhanced) and forebrain-A2AR KO mice (reduced). Thus, A2ARs in glutamatergic corticostriatal terminals and in GABAergic striatal neurons modulate the action of psychostimulants and DARPP-32 phosphorylation in opposite ways. We conclude that A2ARs in glutamatergic terminals prominently control the action of psychostimulants and define a novel mechanism by which A2ARs fine-tune striatal activity by integrating GABAergic, dopaminergic and glutamatergic signaling.
?Dónde se encuentra la prevención y promoción de la salud mental en el momento actual?
García Moratalla,Beatriz;
Revista de la Asociación Espa?ola de Neuropsiquiatría , 2007, DOI: 10.4321/S0211-57352007000200007
Abstract: analyse and historic evolution in the last decades about the primary prevention and promotion of mental health. various proposals for future researchs.
Donación y deliberación: El lugar de la caridad en la ética empresarial
Domingo Moratalla,Agustín;
Veritas , 2010, DOI: 10.4067/S0718-92732010000100001
Abstract: the article discusses some results of the caritas in veritate (civ) to social ethics. a hermeneutic revolutionary contribution because it integrates three basics categories in contemporary ethics: globalization, deliberation and donation. with special attention to the concept of charity in the first and third of the work, first analyzing the presence of this concept in recent social ethics in terms of de-privatization, then reveals the emergence of charity in business ethics. among the contributions that the encyclical makes business ethics, we work in categories what affecting organizational and management methods we have called "new management".
El Parque Agrario: Preservación de la actividad agraria en espacios periurbanos (El caso del Bajo Llobregat) / The agrarian Park: Agrarian activity preservation in periurban areas (The case of the Baix Llobregat)
Ana Zazo Moratalla
Territorios en Formación , 2011,
Abstract: Resumen El interés por la problemática contemporánea de los espacios agrarios periurbanos ha despertado una nueva conciencia urbana que afianza la importancia de la preservación de estos espacios agrarios por sus valores ambientales, culturales y productivos, y que comienza a reaprender las posibles ventajas de su proximidad urbana. Entre ellas, la calidad alimentaria. En el análisis de las respuestas a esta problemática, aparece un uso recurrente del término ‘Parque Agrario’ materializado en diversas propuestas con dispares objetivos, escalas y dimensiones. Para aclarar la confusión del término, se estudia el Parque Agrario del Bajo Llobregat. De este caso se induce la estructura organizativa básica de su figura, analizándola de manera poliédrica y multiescalar. El objeto último del trabajo es valorar la sostenibilidad de la figura en función del resultado de su aplicación a un espacio agrario periurbano, tipológico y predispuesto. Su aplicación y fusión con el espacio agrario periurbano dará lugar a otro ‘concepto aplicado’ de parque, que creará y fortalecerá sus propias redes productivas para introducirse en el ciclo alimentario de la ciudad próxima, bloqueando la base territorial frente al proceso urbano. Palabras clave Preservación, gobernanza, proteccionismo, dinamización agraria, multifuncionalidad, multidimensionalidad territorial. Abstract The interest in contemporary issues of suburban farmland has awakened a new urban consciousness that reinforces the importance of preserving these agrarian areas because of their environmental, cultural and productive values, and starts to re-learn the potential benefits of its proximity to urban areas. Among this potentials, food quality can be found. In the analysis of responses to this problem has found a widespread use of the term 'Agrarian Park' embodied in proposals for different purposes, scales and dimensions. To clarify the confusion of the term, the ‘Parque Agrario del Bajo Llobregat’ has been tested. The basic organizational structure of the figure is induced from thin specific case, analyzing it in a multifaceted and multiscalar way. The ultimate purpose of the study is to assess the sustainability of the figure in the outcome of their application to a suburban agricultural area, typological and biased. Its merge and fusion with the application to a periurban agrarian area, will lead to another ‘concept applied’ park, which will create and strengthen its own production networks to enter in the food cycle of the nearby town, blocking the territorial base opposite the urban process. Keywords Preserv
Ana Zazo Moratalla
Territorios en Formación , 2011,
Dónde se encuentra la prevención y promoción de la salud mental en el momento actual?.
Beatriz García Moratalla
Revista de la Asociación Espa?ola de Neuropsiquiatría , 2007,
Abstract: Análisis y evolución histórica en las últimas décadas en prevención primaria y promoción de la salud. Propuestas para investigaciones futuras.
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