Prolonged fixation and post-mortem delay impede the study of adult neurogenesis in mice.

Adult hippocampal neurogenesis (AHN) gives rise to new neurons throughout life. This phenomenon takes place in more than 120 mammalian species, including humans, yet its occurrence in the latter was questioned after one study proposed the putative absence of neurogenesis markers in the adult human hippocampus. In this regard, we showed that prolonged fixation impedes the visualization of Doublecortin+ immature neurons in this structure, whereas other authors have suggested that a dilated post-mortem delay (PMD) underlies these discrepancies. Nevertheless, the individual and/or additive contribution of fixation and the PMD to the detection (or lack thereof) of other AHN markers has not been studied to date. To address this pivotal question, we used a tightly controlled experimental design in mice, which allowed the dissection of the relative contribution of the aforementioned factors to the visualization of markers of individual AHN stages. Fixation time emerged as the most prominent factor globally impeding the study of this process in mice. Moreover, the visualization of other particularly sensitive epitopes was further prevented by prolonged PMD. These results are crucial to disambiguate current controversies related to the occurrence of AHN not only in humans but also in other mammalian species.

GSK-3ß orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo.

Adult hippocampal neurogenesis enhances brain plasticity and contributes to the cognitive reserve during aging. Adult hippocampal neurogenesis is impaired in neurological disorders, yet the molecular mechanisms regulating the maturation and synaptic integration of new neurons have not been fully elucidated. GABA is a master regulator of adult and developmental neurogenesis. Here we engineered a novel retrovirus encoding the fusion protein Gephyrin:GFP to longitudinally study the formation and maturation of inhibitory synapses during adult hippocampal neurogenesis in vivo. Our data reveal the early assembly of inhibitory postsynaptic densities at 1 week of cell age. Glycogen synthase kinase 3 Beta (GSK-3ß) emerges as a key regulator of inhibitory synapse formation and maturation during adult hippocampal neurogenesis. GSK-3ß-overexpressing newborn neurons show an increased number and altered size of Gephyrin+ postsynaptic clusters, enhanced miniature inhibitory postsynaptic currents, shorter and distanced axon initial segments, reduced synaptic output at the CA3 and CA2 hippocampal regions, and impaired pattern separation. Moreover, GSK-3ß overexpression triggers a depletion of Parvalbumin+ interneuron perineuronal nets. These alterations might be relevant in the context of neurological diseases in which the activity of GSK-3ß is dysregulated.

Response to Comment on "Impact of neurodegenerative diseases on human adult hippocampal neurogenesis".

Rakic and colleagues challenge the use of extensively validated adult hippocampal neurogenesis (AHN) markers and postulate an alternative interpretation of some of the data included in our study. In Terreros-Roncal et al., reconstruction of the main stages encompassed by human AHN revealed enhanced vulnerability of this phenomenon to neurodegenerative diseases. Here, we clarify points and ambiguities raised by these authors.

Response to Comment on "Impact of neurodegenerative diseases on human adult hippocampal neurogenesis".

Alvarez-Buylla and colleagues provide an alternative interpretation of some of the data included in our manuscript and question whether well-validated markers of adult hippocampal neurogenesis (AHN) are related to this phenomenon in our study. In Terreros-Roncal et al., reconstruction of the main stages of human AHN revealed its enhanced vulnerability to neurodegeneration. Here, we clarify ambiguities raised by these authors.

Impact of neurodegenerative diseases on human adult hippocampal neurogenesis.

Disrupted hippocampal performance underlies psychiatric comorbidities and cognitive impairments in patients with neurodegenerative disorders. To understand the contribution of adult hippocampal neurogenesis (AHN) to amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, dementia with Lewy bodies, and frontotemporal dementia, we studied postmortem human samples. We found that adult-born dentate granule cells showed abnormal morphological development and changes in the expression of differentiation markers. The ratio of quiescent to proliferating hippocampal neural stem cells shifted, and the homeostasis of the neurogenic niche was altered. Aging and neurodegenerative diseases reduced the phagocytic capacity of microglia, triggered astrogliosis, and altered the microvasculature of the dentate gyrus. Thus, enhanced vulnerability of AHN to neurodegeneration might underlie hippocampal dysfunction during physiological and pathological aging in humans.

Pain management in Guillain-Barre syndrome: a systematic review.

INTRODUCTION: Pain is a common symptom in patients with Guillain-Barre syndrome. Intensity is moderate to severe in most cases and pain may persist after resolution of the disease. OBJECTIVE: Identify the most appropriate analgesic therapy for pain management in patients with Guillain-Barre syndrome. MATERIAL AND METHODS: Systematic review and selection of scientific articles on treatment of pain in Guillain-Barre syndrome patients, published between January 1985 and December 2012. We included only randomised, double-blind, controlled trials assessing the effectiveness of drugs for pain management in these patients. RESULTS: Four articles met the inclusion criteria. One evaluated the use of gabapentin, another evaluated carbamazepine, a third compared gabapentin to carbamazepine, and the last evaluated use of methylprednisolone. Both carbamazepine and gabapentin were useful for pain management. Patients experienced lower-intensity pain with gabapentin treatment in the study comparing that drug to carbamazepine. Methylprednisolone was not shown to be effective for reducing pain. The published data did not permit completion of a meta-analysis. CONCLUSIONS: There is no robust evidence at present that would point to a single treatment option for this disorder. Further clinical studies of larger patient samples and with a longer duration are needed to characterise types of pain for each patient and measure pain intensity in an objective way.

Dolor neuropático central en enfermedad de Parkinson / Central neuropathic pain in Parkinson's disease

Introducción: El dolor central es uno de los tipos de dolor que se presentan en los pacientes con enfermedad de Parkinson (EP). Debido a que su incidencia y su prevalencia no son elevadas, con frecuencia pasa desapercibido y, por consiguiente, los pacientes afectados no reciben tratamiento analgésico adecuado, lo cual incrementa su padecimiento. Este dolor es de tipo quemante, de inicio espontáneo, con periodos de exacerbación, pobremente localizado y usualmente más intenso en el lado motor más afectado. Su fisiopatología aún no está claramente definida. Desarrollo: Se realizaron una búsqueda y una selección sistemática de los estudios clínicos realizados en pacientes con EP, entre enero de 1986 y septiembre de 2010, que evaluaron el dolor neuropático central primario.Conclusiones: No se ha demostrado que el tratamiento con L-Dopa tenga efectos analgésicos sobre este dolor. Se requieren estudios futuros que permitan un mejor conocimiento de esta patología, para desarrollar mecanismos de prevención y tratamiento de esta enfermedad (AU)

Introduction: Central pain is one type of pain that occurs in patients with Parkinson's disease (PD). Because of its low incidence and prevalence, it often goes unnoticed and affected patients do not therefore receive adequate analgesic therapy, which increases their suffering. It is a burning pain with spontaneous onset and periods of exacerbation; pain is poorly localised and usually more intense on the more affected side. Its pathophysiology on patients with PD is not clearly defined. Methods: We performed a search and systematic selection of all clinical studies published from January 1986 to September 2010 concerning central neuropathic pain in Parkinson's disease. Conclusions: Treatment with L-Dopa has not been demonstrated to have an analgesic effect on this type of pain. Future studies are required to improve our understanding of this condition, and to develop interventions for preventing and treating it (AU)

Central neuropathic pain in Parkinson's disease.

INTRODUCTION: Central pain is one type of pain that occurs in patients with Parkinson's disease (PD). Because of its low incidence and prevalence, it often goes unnoticed and affected patients do not therefore receive adequate analgesic therapy, which increases their suffering. It is a burning pain with spontaneous onset and periods of exacerbation; pain is poorly localised and usually more intense on the more affected side. Its pathophysiology on patients with PD is not clearly defined. METHODS: We performed a search and systematic selection of all clinical studies published from January 1986 to September 2010 concerning central neuropathic pain in Parkinson's disease. CONCLUSIONS: Treatment with L-Dopa has not been demonstrated to have an analgesic effect on this type of pain. Future studies are required to improve our understanding of this condition, and to develop interventions for preventing and treating it.

Sleep evaluation scales and questionaries: a review.

INTRODUCTION: Whenever a new scale is created or translated from another language, it must be validated, establishing its reliability for the new population where it will be used. Sleep quality concept is a construct that can be evaluated using self-report scales. Resulting elements vary depending on the individuals surveyed. This type of evaluation is mainly subjective and includes quantitative aspects such as sleep duration, number of awakenings, latency time, and qualitative aspects such as rest sensation, mood and oneiric content (Valencia, 2000). In the present study we made a critical review of the sleep scales designed for child, adolescent and adult populations that have been validated and the difficulties they might present. METHODOLOGY: Between September 2005 and May 2006 a bibliographical search was made within Pubmed, Ovid and the data base of the periodical and book library of the Ramon de la Fuente Muñiz National Institute of Psychiatry, using and combining the following key words: sleep, sleep questionnaire, sleep scale, sleep inventory, adolescent, adolescent sleep scale. The most relevant papers to our study were selected. The search was limited to Spanish and English articles, although there was no year or geographical origin limit. Articles that did not include clinimetrical data where excluded. CONCLUSIONS: Based on our bibliographical search and our discussion, we suggested the design and validation of a Spanish scale to evaluate adolescent population which avoids a time interval between awakening and the answering of the instrument in order to decrease recall bias.

[Zinc and epilepsy: is there a causal relation between them?]. / Zinc y epilepsia: existe una relación causal?

INTRODUCTION: Zinc is a fundamental trace element for an adequate nervous system function. It has been suggested that in the brain, a zinc homeostasis alteration may be associated with the genesis of epilepsy, although it is not yet determined if concentrations of zinc are a cause or a consequence of seizures. Another poorly studied aspect is the relationship between antiepileptic drugs and the neuronal zinc behaviour. DEVELOPMENT: We perform a systematic review of the literature to evaluate the role that zinc plays in epilepsy as well as the antiepileptic effect of zinc concentrations. Databases such as MEDLINE, EMBASE, SCISEARCH and LILACS were consulted from January 1974 to July 2005. All articles published in English and Spanish were considered. A manual review of the references present in each article was done in order to identify the articles that the electronic search may have not found itself. The title and abstract of the potential articles were analyzed before asking for the complete article. However, articles that seemed ambiguous were completely analyzed later to establish their relevance. CONCLUSIONS: Clinical research in epilepsy presented contradictory results. In fact, the reviewed studies, both animal and human, did not give enough evidence to determine if organic zinc variations are directly related to epilepsy. Most of them gave not statistically significant results.

Intoxicación por escopolamina (‘burundanga’): pérdida de la capacidad de tomar decisiones / Scopolamine poisoning ("burudanga"): loss of the ability to make decisions

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[Changes in selenium levels in epilepsy]. / Alteración de la concentración de selenio en la epilepsia.

INTRODUCTION: It has been suggested that antiepileptic drug therapies deplete total body selenium stores and failure to give appropriate selenium supplementation, especially to patients receiving valproic acid during pregnancy may increase the risk of neural tube defects or other free radical mediated damage. Selenium is essential for the synthesis of selenoproteins, including glutathione peroxidase. AIMS: To review the present state of knowledge about selenium behaviour in people with epilepsy taking antiepileptic drugs and to develop guidelines for the appropriate use of selenium supplements. DEVELOPMENT: Databases such as Medline, Embase, Scisearch and Lilacs were consulted to have access to literature. A search in said databases was performed in order to find articles published from January 1966 to August 2004. All articles published in English and Spanish were considered. A manual review of the references present in each produced article was done in order to identify the articles that the electronic search may have not found itself. The title and abstract of the potential articles were analyzed before asking for the complete article. However, articles which seemed ambiguous were completely analyzed later to establish their relevance. CONCLUSIONS: There is insufficient evidence to fully evaluate the effect of selenium supplementation. The possible beneficial effects on pregnancy need to be evaluated in further studies.

Alteración de la concentración de selenio en la epilepsia / Changes in selenium levels in epilepsy

Introducción. Se ha sugerido que los tratamientos anticonvulsionantes disminuyen las reservas de selenio en el organismo y que no administrar suplementos de selenio, especialmente a las pacientes que reciben ácido valproico durante el embarazo, puede aumentar el riesgo de desarrollar defectos del tubo neural u otras alteraciones mediadas por radicales libres. El selenio es un oligoelemento esencial para la síntesis de selenoproteínas, incluida la glutatión peroxidasa. Objetivo. Realizar una revisión sistemática de la literatura para poder presentar el estado del conocimiento sobre el comportamiento del selenio en los pacientes con epilepsia en tratamiento anticonvulsionante y desarrollar unas recomendaciones para el uso adecuado de un suplemento de selenio. Desarrollo. Se consultaron las bases de datos Medline, Embase, Scisearch y Lilacs para acceder a la literatura, y se realizó una búsqueda para localizar artículos publicados entre enero de 1966 y agosto de 2004. Se tomaron todos los artículos publicados en inglés y español. Se realizó una revisión manual de las referencias presentadas en cada artículo con el fin de identificar los que no identificó la búsqueda electrónica. El título y el resumen de los artículos potencialmente útiles se analizaban antes de solicitar el artículo completo. Sin embargo, los artículos en los que éstos eran ambiguos para determinar su pertinencia también se analizaron en su totalidad. Conclusiones. No hay suficientes evidencias para evaluar el efecto de administrar un suplemento de selenio. El posible beneficio durante el embarazo requiere estudios más profundos

Introduction. It has been suggested that antiepileptic drug therapies deplete total body selenium stores and failure to give appropriate selenium supplementation, especially to patients receiving valproic acid during pregnancy may increase the risk of neural tube defects or other free radical mediated damage. Selenium is essential for the synthesis of selenoproteins, including glutathione peroxidase. Aims. To review the present state of knowledge about selenium behaviour in people with epilepsy taking antiepileptic drugs and to develop guidelines for the appropriate use of selenium supplements. Development. Databases such as Medline, Embase, Scisearch and Lilacs were consulted to have access to literature. A search in said databases was performed in order to find articles published from January 1966 to August 2004. All articles published in English and Spanish were considered. A manual review of the references present in each produced article was done in order to identify the articles that the electronic search may have not found itself. The title and abstract of the potential articles were analyzed before asking for the complete article. However, articles which seemed ambiguous were completely analyzed later to establish their relevance. Conclusions. There is insufficient evidence to fully evaluate the effect of selenium supplementation. The possible beneficial effects on pregnancy need to be evaluated in further studies