Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems. © 2010 Elsevier Inc.

O antagonismo do receptor de serotonina do tipo 7 da substância cinzenta periaquedutal dorsal reduz a ansiedade experimental basal, mas não aquela gerada pela retirada do etanol em ratos

Ethanol-dependent individuals who reduce or discontinue its use may present Alcohol Withdrawal Syndrome, which is characterized by unpleasant signs and symptoms, such as anxiety, that may trigger relapses. Ethanol, a psychotropic drug, is able to promote behavioral and neurophysiological changes, acting on different neurotransmitter systems, including the serotonergic, which has also been directly associated with aversive states, including anxiety. This study aimed to investigate the participation of type 7 serotonin receptor (5-HT7) of the dorsal periaqueductal gray (DPAG) on basal experimental anxiety and that caused by ethanol withdrawal. For this, 75-100 days old Wistar rats were subjected to two experiments. On the first one, animals underwent stereotactic surgery for implantation of guide cannulas used for administration of the drug directly into the DPAG. After seven days, the animals received doses of 2.5; 5 and 10 nmols of type 7 receptor antagonist SB269970 (SB) or vehicle intra-DPAG and, ten minutes after, they were exposed to elevated plus maze (EPM). In the following day, the animals were submitted to the same treatment and tested in the open field (OF). In the second experiment, animals received increasing concentrations (2%, 4%, 6%) of ethanol as the only source of liquid diet or water (control group), both with free access to chow. Seventy two hours and ninety six hours after the ethanol withdrawal, animals received SB (2.5 and 5.0 nmols) intraDPAG ten minutes before the test in the LCE and OF, respectively. In experiment 1, the dose of antagonist 10 nmols was able of reversing the anxiety generated by EPM. In the experiment 2, ineffective SB doses on the LCE (2.5 and 5.0 nmol) were not able to reverse the anxiety caused by the ethanol withdrawal in the EPM, although the dose of 2.5 nmols of SB has reversed its hipolocomotor effect in this test. This result suggests that the 5-HT7 receptor is involved in the modulation of the basal experimental anxiety in rats, but not in the anxiety caused by ethanol withdrawal in the DPAG.

Avaliação dos efeitos da retirada do etanol em curto e longo prazo sobre respostas comportamentais relacionadas à ansiedade e sobre células imunorreativas para a serotonina no núcleo dorsal da Rafe em ratas

Ethanol withdrawn individuals present a wealth of signs and symptoms, some of them related with anxiety. To better understand brain areas involved in anxiety caused by ethanol abstinence, preclinical studies have been employing models of ethanol consumption followed by withdrawal in rodents submitted to behavioral tests of anxiety, such as the elevated plus-maze. The aim of this study was to investigate if short- or long-term ethanol withdrawal could alter both anxiety-related behaviors in the elevated plus-maze (EPM) and open field tests and the number of serotonin immunorreactive cels in the dorsal raphe nucleus, a midbrain area associated with anxiety. Female Wistar rats (90 days old) were submitted to increasing concentrations of ethanol (2% for 3 days, 4% for 3 days and 6% for 15 days) as the only source of liquid diet and the control group received water ad libitum. Both groups received food ad libitum. In the behavioral experiments, on 21st day of consumption, ethanol was substituted by water (withdrawal) and 72 h or 21 days after withdrawal animals were submitted to the EPM, where it was evaluated the percentage of time and entries in the open arms and the entries in the enclosed arms during 5 minutes. Twenty and four hours after testing in the EPM, animals were submitted to the open field test for 15 minutes, where the distance traveled by the animals was observed along this period. During the first 5 minutes, the distance traveled, entries and time spent in the center of the test were analyzed. In the immunohistochemistry study, animals were submitted to 21 days of consumption of ethanol followed or not by 72 hours and 21 days of withdrawal previously perfusion, brain tissue preparation and quantification of serotonin dyed cells in the dorsal and caudal portions in the dorsal raphe nucleus. Behavioral data showed that both short- and long-term ethanol withdrawals reduced the open arms exploration in the EPM. In the open field test there were no locomotor activity changes during the total 15 minutes; however, longterm ethanol withdrawal reduced the exploration in the center of the open field during the first 5 minutes. In the immunohistochemistry step, there were no differences, when short- and long-term withdrawn groups were compared with control group; nevertheless, the chronic consumption of ethanol decreased the number of serotonergic immunorreactive cells in the dorsal part of dorsal raphe nucleus. Taken together, results here obtained suggest that both short- and long-term ethanol withdrawals promoted an anxiogenic-like effect that was not related with changes in the serotonin immunorreactivity in the dorsal and caudal parts of the dorsal raphe nucleus.

Mécanismes de guidage des axones sérotoninergiques du raphé dorsal : études in vivo et in vitro

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Expression des récepteurs EphA dans le raphé dorsal néonatal et adulte

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Contributions of Dorsal/Ventral Hippocampus and Dorsolateral/Dorsomedial Striatum to Interval Timing

Humans and animals have remarkable capabilities in keeping time and using time as a guide to orient their learning and decision making. Psychophysical models of timing and time perception have been proposed for decades and have received behavioral, anatomical and pharmacological data support. However, despite numerous studies that aimed at delineating the neural underpinnings of interval timing, a complete picture of the neurobiological network of timing in the seconds-to-minutes range remains elusive. Based on classical interval timing protocols and proposing a Timing, Immersive Memory and Emotional Regulation (TIMER) test battery, the author investigates the contributions of the dorsal and ventral hippocampus as well as the dorsolateral and the dorsomedial striatum to interval timing by comparing timing performances in mice after they received cytotoxic lesions in the corresponding brain regions. On the other hand, a timing-based theoretical framework for the emergence of conscious experience that is closely related to the function of the claustrum is proposed so as to serve both biological guidance and the research and evolution of “strong” artificial intelligence. Finally, a new “Double Saturation Model of Interval Timing” that integrates the direct- and indirect- pathways of striatum is proposed to explain the set of empirical findings.

Mécanismes de guidage des axones sérotoninergiques du raphé dorsal : études in vivo et in vitro

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Expression des récepteurs EphA dans le raphé dorsal néonatal et adulte

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Proliferative Defects and Formation of a Double Cortex in Mice Lacking Mltt4 and Cdh2 in the Dorsal Telencephalon

Radial glial cells (RGCs) in the ventricular neuroepithelium of the dorsal telencephalon are the progenitor cells for neocortical projection neurons and astrocytes. Here we showthatthe adherens junction proteins afadin and CDH2 are criticalforthe control of cell proliferation in the dorsal telencephalon and for the formation of its normal laminar structure. Inactivation of afadin or CDH2 in the dorsal telenceph-alon leads to a phenotype resembling subcortical band heterotopia, also known as “double cortex,” a brain malformation in which heterotopic gray matter is interposed between zones of white matter. Adherens junctions between RGCs are disrupted in the mutants, progenitor cells are widely dispersed throughout the developing neocortex, and their proliferation is dramatically increased. Major subtypes of neocortical projection neurons are generated, but their integration into cell layers is disrupted. Our findings suggest that defects in adherens junctions components in mice massively affects progenitor cell proliferation and leads to a double cortex-like phenotype.

Comparación de la evolución en pacientes con diagnóstico de espasmo muscular en región cervical, dorsal y lumbar, atendidos con masaje manual y pacientes tratados con vibroterapia en las edades de 20 a 70 años de ambos sexos, atendidos en el Hospital Nacional de San Francisco Gotera, departamento de Morazán, en el período de julio a septiembre de 2007.

La investigación se realizó en pacientes con diagnóstico de Espasmo Muscular en región Cervical, Dorsal y Lumbar entre las edades de 20 a 70 años de ambos sexos, atendidos en el Hospital Nacional de San Francisco Gotera, en el período de Julio a Septiembre de 2007, con el objetivo de establecer la comparación de la evolución entre los pacientes atendidos con Masaje Manual y los tratados con Vibroterapia. La muestra estuvo constituida por un total de 12 pacientes, la cual se dividió en dos grupos de 6 pacientes cada uno, en donde se atendió a un grupo con Masaje manual y el otro fue tratado con Vibroterapia. El tipo de estudio aplicado fue prospectivo y comparativo, las técnicas de obtención de información empleadas fueron la Documental como la bibliografía y la de Campo como la entrevista; la primera permitió realizar una amplia revisión de libros y diccionarios y la segunda fue destinada a la población en estudio con el fin de obtener información del estado real del paciente.

Proliferative Defects and Formation of a Double Cortex in Mice Lacking Mltt4 and Cdh2 in the Dorsal Telencephalon

Radial glial cells (RGCs) in the ventricular neuroepithelium of the dorsal telencephalon are the progenitor cells for neocortical projection neurons and astrocytes. Here we showthatthe adherens junction proteins afadin and CDH2 are criticalforthe control of cell proliferation in the dorsal telencephalon and for the formation of its normal laminar structure. Inactivation of afadin or CDH2 in the dorsal telenceph-alon leads to a phenotype resembling subcortical band heterotopia, also known as “double cortex,” a brain malformation in which heterotopic gray matter is interposed between zones of white matter. Adherens junctions between RGCs are disrupted in the mutants, progenitor cells are widely dispersed throughout the developing neocortex, and their proliferation is dramatically increased. Major subtypes of neocortical projection neurons are generated, but their integration into cell layers is disrupted. Our findings suggest that defects in adherens junctions components in mice massively affects progenitor cell proliferation and leads to a double cortex-like phenotype.

Radiofrecuencia pulsada sobre el nervio dorsal del pene: tratamiento eficaz para la neuralgia refractaria del pudendo

La neuralgia del pudendo se define como un síndrome doloroso neuropático, que involucra al dermatomo y a la inervación motora del nervio pudendo. Cualquier punto de su trayecto, desde su origen hasta sus ramificaciones terminales, es susceptible de sufrir diferentes grados de afectación o lesión. La localización del dolor puede ser perineal, rectal o en el área del clítoris/pene, presentándose de forma unilateral o bilateral; se agrava al sentarse y disminuye o desaparece al estar de pie; habitualmente respeta el descanso nocturno y puede asociarse a disfunción urinaria, anal e incluso sexual. Son múltiples las causas que pueden provocar la afectación del nervio pudendo, como partos, caídas, golpes directos y cirugías pélvicas. Esta patología constituye una entidad relativamente frecuente en las unidades de dolor crónico. Son varias las terapias utilizadas, incluyendo fármacos, bloqueos nerviosos del pudendo, cirugía descompresiva y neuromodulación de cordones posteriores medulares. Presentamos el caso de un paciente que, tras ser sometido a prostatectomía radical, consultó por dolor crónico continuo de tipo quemante junto a crisis lancinantes en parte distal derecha del pene (territorio del pudendo) y en el que aplicamos radiofrecuencia pulsada sobre el nervio dorsal derecho del pene obteniendo un buen resultado. Son varios los autores que han publicado tratamientos exitosos con radiofrecuencia pulsada del pudendo para el tratamiento de la neuralgia de dicho nervio, pero hasta ahora no se ha publicado ningún artículo de radiofrecuencia pulsada sobre los nervios dorsales del pene.

El colgajo fasciocutáneo dorsal ulnar en quemaduras eléctricas de la mano: un colgajo constante, rápido y seguro

Antecedentes y Objetivos. La extremidad superior es el área más frecuentemente afectada en las quemaduras eléctricas de alto voltaje, con una alta tasa de amputaciones, síndromes compartimentales y defectos de partes blandas que precisan cobertura. La literatura en cuanto a la cirugía reconstructiva de la mano con quemaduras eléctricas es escasa, pero es fundamental en la fase aguda establecer un plan quirúrgico y una cobertura estable de estos frecuentes defectos en mano y muñeca. Pacientes y Método. Empleamos el colgajo fasciocutáneo dorsal ulnar en 3 pacientes con defectos cutáneos en muñeca secundarios a quemaduras eléctricas de alto voltaje, durante la fase aguda de estas lesiones. Resultados. Obtuvimos en todos los casos una cobertura estable y de alta calidad y sin registrar complicaciones relacionadas con el colgajo o con la zona donante. Conclusiones. Debido a la constancia de su pedículo, la rapidez y seguridad de su disección y la preservación de ambos ejes arteriales, el colgajo fasciocutáneo dorsal ulnar es una herramienta de primer uso en la cobertura de los defectos de la mano y de la muñeca tras quemaduras eléctricas de alto voltaje.