A study of epileptogenic network structures in rat hippocampal cultures using first spike latencies during synchronization events

Study of hypersynchronous activity is of prime importance for combating epilepsy. Studies on network structure typically reconstruct the network by measuring various aspects of the interaction between neurons and subsequently measure the properties of the reconstructed network. In sub-sampled networks such methods lead to significant errors in reconstruction. Using rat hippocampal neurons cultured on a multi-electrode array dish and a glutamate injury model of epilepsy in vitro, we studied synchronous activity in neuronal networks. Using the first spike latencies in various neurons during a network burst, we extract various recurring spatio-temporal onset patterns in the networks. Comparing the patterns seen in control and injured networks, we observe that injured networks express a wide diversity in their foci (origin) and activation pattern, while control networks show limited diversity. Furthermore, we note that onset patterns in glutamate injured networks show a positive correlation between synchronization delay and physical distance between neurons, while control networks do not.

A study of epileptogenic network structures in rat hippocampal cultures using first spike latencies during synchronization events

Study of hypersynchronous activity is of prime importance for combating epilepsy. Studies on network structure typically reconstruct the network by measuring various aspects of the interaction between neurons and subsequently measure the properties of the reconstructed network. In sub-sampled networks such methods lead to significant errors in reconstruction. Using rat hippocampal neurons cultured on a multi-electrode array dish and a glutamate injury model of epilepsy in vitro, we studied synchronous activity in neuronal networks. Using the first spike latencies in various neurons during a network burst, we extract various recurring spatio-temporal onset patterns in the networks. Comparing the patterns seen in control and injured networks, we observe that injured networks express a wide diversity in their foci (origin) and activation pattern, while control networks show limited diversity. Furthermore, we note that onset patterns in glutamate injured networks show a positive correlation between synchronization delay and physical distance between neurons, while control networks do not.

Improvement in Bone Properties by Using Risedronate Adsorbed Hydroxyapatite Novel Nanoparticle Based Formulation in a Rat Model of Osteoporosis

A superior drug formulation capable of achieving efficient osteogenesis is in imperative demand for the treatment of osteoporosis. In the present study we investigated the potential of using novel risedronate-hydroxyapatite (HA) nanoparticle based formulation in an animal model of established osteoporosis. Nanoparticles of HA loaded with risedronate (NHLR) of various sizes (80-130 nm) were generated for bone targeted drug delivery. Three months after ovariectomy, 36 ovariectomized (OVX) rats were divided into 6 equal groups and treated with various doses of NHLR (500,350 and 250 mu g/kg intravenous single dose) and sodium risedronate (500 mu g/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. One month after drug administration, the left tibia and femur were tested for bone mechanical properties and histology, respectively. In the right femur, bone density was measured by method based on Archimedes principle and bone porosity analyses were performed using X-ray imaging. NHLR (250 mu g/kg) showed a significant increase in bone density and reduced bone porosity when compared with OVX control. Moreover, NHLR (250 mu g/kg) significantly increased bone mechanical properties and bone quality when compared with OVX control. The results strongly suggest that the NHLR, which is a novel nanoparticle based formulation, has a therapeutic advantage over risedronate sodium monotherapy for the treatment of osteoporosis in a rat model of postmenopausal osteoporosis.

Potential ultrastructural changes in rat epididymal cell types induced by Boswellia papyrifera and Boswellia carterii incense

Boswellia papyrifera and Boswellia carterii, known as Arabian incense, diffuses smoke, contaminating the air, which adversely affects human health. Therefore, this study was designed to ascertain the effect of these plants on histopathological and ultrastructure changes in cauda epididymis of Albino rats. Animals were exposed to 4 g/kg body weight of B. papyrifera and B. carterii daily for 120 days along with suitable controls. Our study indicates a significant reduction in epithelial heights. Cells showed signs of degeneration. The ultrastructural study revealed that the cauda epididymis was affected, including its cell types. Furthermore, a decrease in the size of mitochondria, Golgi complex, and both ERs was observed. In all treated groups, plasma fructose decreased considerably, indicating the sign of reduced energy, vital for motility and other sperm functions. The results of this study suggest that these plants systematically affect cauda epididymal cell types and its lumen through its potential toxicity. (C) 2013 Published by Elsevier Masson SAS on behalf of Academie des sciences.

Functional analysis of ultra high information rates conveyed by rat vibrissal primary afferents

Sensory receptors determine the type and the quantity of information available for perception. Here, we quantified and characterized the information transferred by primary afferents in the rat whisker system using neural system identification. Quantification of ``how much'' information is conveyed by primary afferents, using the direct method (DM), a classical information theoretic tool, revealed that primary afferents transfer huge amounts of information (up to 529 bits/s). Information theoretic analysis of instantaneous spike-triggered kinematic stimulus features was used to gain functional insight on ``what'' is coded by primary afferents. Amongst the kinematic variables tested-position, velocity, and acceleration-primary afferent spikes encoded velocity best. The other two variables contributed to information transfer, but only if combined with velocity. We further revealed three additional characteristics that play a role in information transfer by primary afferents. Firstly, primary afferent spikes show preference for well separated multiple stimuli (i.e., well separated sets of combinations of the three instantaneous kinematic variables). Secondly, neurons are sensitive to short strips of the stimulus trajectory (up to 10 ms pre-spike time), and thirdly, they show spike patterns (precise doublet and triplet spiking). In order to deal with these complexities, we used a flexible probabilistic neuron model fitting mixtures of Gaussians to the spike triggered stimulus distributions, which quantitatively captured the contribution of the mentioned features and allowed us to achieve a full functional analysis of the total information rate indicated by the DM. We found that instantaneous position, velocity, and acceleration explained about 50% of the total information rate. Adding a 10 ms pre-spike interval of stimulus trajectory achieved 80-90%. The final 10-20% were found to be due to non-linear coding by spike bursts.

Ultrastructural and hormonal changes in rat cauda epididymal spermatozoa induced by Boswellia papyrifera and Boswellia carterii

Boswellia papyrifera and Boswellia carterii diffuses smoke polluting air that adversely affects indoor environment that certainly harm human health. Therefore, this study aims at ascertaining the effect of these plants on gonadal hormones and molecular changes in rat spermatozoa. The animals were exposed to 4 g/kg body weight of B. papyrifera and B. carterii daily for 120 days along with suitable controls. Significant decreases in FSH, LH and testosterone levels were evidenced, along with a reduction of protein, sialic acid, and carnitine levels. In sperm physiology, sperm count, motility, speed decrease, whereas sperm anomalies increase. TEM observation indicates morphological changes in plasma and acrosomal membranes, cytoplasmic droplet in the tail region, vacuolated, and disorganization of the mitochondrial sheath. These findings demonstrate that B. papyrifera and B. carterii smoke affects the process of sperm formation and maturation, which indicates the detrimental effects of these plants on the reproductive system. (c) 2014 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.d

Tonic current through GABAA receptors and hyperpolarization-activated cyclic nucleotide-gated channels modulate resonance properties of rat subicular pyramidal neurons

The subiculum, considered to be the output structure of the hippocampus, modulates information flow from the hippocampus to various cortical and sub-cortical areas such as the nucleus accumbens, lateral septal region, thalamus, nucleus gelatinosus, medial nucleus and mammillary nuclei. Tonic inhibitory current plays an important role in neuronal physiology and pathophysiology by modulating the electrophysiological properties of neurons. While the alterations of various electrical properties due to tonic inhibition have been studied in neurons from different regions, its influence on intrinsic subthreshold resonance in pyramidal excitatory neurons expressing hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is not known. Using pharmacological agents, we show the involvement of alpha 5 beta gamma GABA(A) receptors in the picrotoxin-sensitive tonic current in subicular pyramidal neurons. We further investigated the contribution of tonic conductance in regulating subthreshold electrophysiological properties using current clamp and dynamic clamp experiments. We demonstrate that tonic GABAergic inhibition can actively modulate subthreshold properties, including resonance due to HCN channels, which can potentially alter the response dynamics of subicular pyramidal neurons in an oscillating neuronal network.

In vitro exposure of tobacco specific nitrosamines decreases the rat lung phospholipids by enhanced phospholipase A(2) activity

Tobacco-specific nitrosamines (TSNA) have implications in the pathogenesis of various lung diseases and conditions are prevalent even in non-smokers. N-nitrosonornicotine (NNN) and 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are potent pulmonary carcinogens present in tobacco product and are mainly responsible for lung cancer. TSNA reacts with pulmonary surfactants, and alters the surfactant phospholipid. The present study was undertaken to investigate the in vitro exposure of rat lung tissue slices to NNK or NNN and to monitor the phospholipid alteration by P-32]orthophosphate labeling. Phospholipid content decreased significantly in the presence of either NNK or NNN with concentration and time dependent manner. Phosphatidylcholine (PC) is the main phospholipid of lung and significant reduction was observed in PC similar to 61%, followed by phosphatidylglycerol (PG) with 100 mu M of NNK, whereas NNN treated tissues showed a reduction in phosphatidylserine (PS) similar to 60% and PC at 250 mu M concentration. The phospholipase A(2) assays and expression studies reveal that both compounds enhanced phospholipid hydrolysis, thereby reducing the phospholipid content. Collectively, our data demonstrated that both NNK and NNN significantly influenced the surfactant phospholipid level by enhanced phospholipase A(2) activity. (C) 2014 Elsevier Ltd. All rights reserved.

Depression biased non-Hebbian spike-timing-dependent synaptic plasticity in the rat subiculum

The subiculum is a structure that forms a bridge between the hippocampus and the entorhinal cortex (EC), and plays a major role in the memory consolidation process. Here, we demonstrate spike-timing-dependent plasticity (STDP) at the proximal excitatory inputs on the subicular pyramidal neurons of juvenile rat. Causal (positive) pairing of a single EPSP with a single back-propagating action potential (bAP) after a time interval of 10 ms (+10 ms) failed to induce plasticity. However, increasing the number of bAPs in a burst to three, at two different frequencies of 50 Hz (bAP burst) and 150 Hz, induced long-term depression (LTD) after a time interval of +10 ms in both the regular-firing (RF), and the weak burst firing (WBF) neurons. The LTD amplitude decreased with increasing time interval between the EPSP and the bAP burst. Reversing the order of the pairing of the EPSP and the bAP burst induced LTP at a time interval of -10 ms. This finding is in contrast with reports at other synapses, wherein prebefore postsynaptic (causal) pairing induced LTP and vice versa. Our results reaffirm the earlier observations that the relative timing of the pre- and postsynaptic activities can lead to multiple types of plasticity profiles. The induction of timing-dependent LTD (t-LTD) was dependent on postsynaptic calcium change via NMDA receptors in the WBF neurons, while it was independent of postsynaptic calcium change, but required active L-type calcium channels in the RF neurons. Thus the mechanism of synaptic plasticity may vary within a hippocampal subfield depending on the postsynaptic neuron involved. This study also reports a novel mechanism of LTD induction, where L-type calcium channels are involved in a presynaptically induced synaptic plasticity. The findings may have strong implications in the memory consolidation process owing to the central role of the subiculum and LTD in this process.

Lobe-specific Expression of Phosphodiesterase 5 in Rat Prostate

OBJECTIVE To investigate the level and location of phosphodiesterase 5 (PDE5) expression in rat prostate. METHODS The ventral, dorsal, and lateral lobes of rat prostate were examined for PDE5 expression by Western blotting. Intact rat urogenital complex, including the urinary bladder and accessory reproductive glands, was examined for PDE5 expression by immunohistochemistry. Individual prostatic lobes were further examined by immunofluorescence for expression of PDE5, alpha-smooth muscle actin, and rat endothelial cell antigen. RESULTS Western blot analysis showed that PDE5 was expressed at a significantly lower level in dorsal lobe (DL) than in ventral lobe (VL) or lateral lobe (LL). Immunohistochemistry and immunofluorescence analyses showed that PDE5 was expressed in both acinar epithelium and periacinar smooth muscle. However, although similar levels of smooth muscle PDE5 expression were observed in all 3 prostatic lobes, significantly lower level of epithelial PDE5 expression was found in DL compared with VL or LL. In prostatic blood vessels, PDE5 expression was clearly visible in the endothelium but not as easily detectable in the smooth muscle. CONCLUSION PDE5 was expressed in the acinar epithelium and periacinar smooth muscle of rat prostate. However, the epithelial PDE5 expression was significantly less in DL than in VL or LL. Regardless, the acinar wall, not the blood vessel wall, is the predominant PDE5 expression site in rat prostate. (C) 2015 Elsevier Inc.

Potential histopathological and molecular changes in rat vas deferens inhaled by Boswellia papyrifera and Boswellia carterii

Boswellia papyrifera and Boswellia carterii released from smoke contaminate indoor environment and consequently adversely affect humans as evidenced by respiratory disturbances. The aim of this study was to determine the effects of these plants on pathological and biochemical changes in vas deferens of albino rats. Animals were administered 4g/kg body weight B. papyrifera and B. carterii daily for 120days along with controls. Significant changes were observed in epithelial cell types and some cells showed signs of degeneration. The ultrastructural studies revealed marked changes in cytoplasmic organelles. Microvilli were missing and lysosomes were found in the cytoplasm. In addition, all treated groups plasma fructose and other biochemical parameters were decreased indicating reduced energy necessary for motility and contractility of spermatozoa. Many spermatozoa were disorganized and agglomerated. Data suggest that smoke from these plants adversely affects vas deferens.

Activation of InsP(3) receptors is sufficient for inducing graded intrinsic plasticity in rat hippocampal pyramidal neurons

The synaptic plasticity literature has focused on establishing necessity and sufficiency as two essential and distinct features in causally relating a signaling molecule to plasticity induction, an approach that has been surprisingly lacking in the intrinsic plasticity literature. In this study, we complemented the recently established necessity of inositol trisphosphate (InsP(3)) receptors (InsP(3)R) in a form of intrinsic plasticity by asking if InsP(3)R activation was sufficient to induce intrinsic plasticity in hippocampal neurons. Specifically, incorporation of D-myo-InsP(3) in the recording pipette reduced input resistance, maximal impedance amplitude, and temporal summation but increased resonance frequency, resonance strength, sag ratio, and impedance phase lead. Strikingly, the magnitude of plasticity in all these measurements was dependent on InsP 3 concentration, emphasizing the graded dependence of such plasticity on InsP(3)R activation. Mechanistically, we found that this InsP(3)-induced plasticity depended on hyperpolarization-activated cyclic nucleotide-gated channels. Moreover, this calcium-dependent form of plasticity was critically reliant on the release of calcium through InsP(3)Rs, the influx of calcium through N-methyl-D-aspartate receptors and voltage-gated calcium channels, and on the protein kinase A pathway. Our results delineate a causal role for InsP(3)Rs in graded adaptation of neuronal response dynamics, revealing novel regulatory roles for the endoplasmic reticulum in neural coding and homeostasis.

Effect of combined treatment with zoledronic acid and propranolol on mechanical strength in an rat model of disuse osteoporosis

Objectives: A model that uses right hind-limb unloading of rats is used to study the consequences of skeletal unloading during various conditions like space flights and prolonged bed rest in elderly. This study was aimed to investigate the additive effects of antiresorptive agent zoledronic acid (ZOL), alone and in combination with propranolol (PRO) in a rat model of disuse osteoporosis. Methods: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were randomized into four groups: 1-RHLI positive control, 2-RHLI plus ZOL (50 mu g/kg, i.v. single dose), 3-RHLI plus PRO (0.1 mg/kg, s.c. 5 days per week), 4-RHLI plus PRO (0.1 mg/kg, s.c. 5 days per week) plus ZOL (50 mu g/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. Results: With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment with ZOL plus PRO was more effective than ZOL or PRO monotherapy. Moreover, combination therapy using ZOL plus PRO was more effective in improving dry bone weight and preserved the cortical bone porosity better than monotherapy using ZOL or PRO in right hind-limb immobilized rats. Conclusions: These data suggest that this combined treatment with ZOL plus PRO should be recommended for the treatment of disuse osteoporosis. (C) 2014 Elsevier Editora Ltda. All rights reserved.

Evaluación final del Proyecto capacitación popular sobre el manejo del agroecosistema del trópico húmedo (PTH), Pancasan-Matagalpa, 1993-1996

El presente trabajo se realizó con el objetivo de Evaluar los resultados alcanzados por el Proyecto del Trópico Húmedo e:n la Zona de Pancasan del Departamento de Matagalpa quien fuera ejecutado por la Asociación Agrícola para el Desarrollo Agrícola Comunal (ADDAC) durante la segunda fase de ejecución del Proyecto, comprendida desde Septiembre de 1993 a Febrero de 1996, flnanciado por la Agencia Noruega para el Desarrollo (NORAD). La metodología empleada en el presente Estudio se basó en el tipo de Evaluación Ex­ post de la Dirección de Proyectos y Programación de Inversiones de las Naciones Unidas CEPAL y se resume en cuatro etapas: - Primera etapa Revisión de Información Escrita. - Segunda etapa Levantado de Datos de Campo. - Tercera etapa Procesamiento y Análisis de la Información de Campo. - Cuata y última etapa Elaboración y Presentacion del Informe Final. Los resultados alcanzados por el proyecto según el estudio, muestra que los ingresos percibidos por los productores participantes del Proyecto o Poblacion Meta (PM) se consideran que han aumentado en un 40% más con la incidencia del Proyecto Trópico Húmedo (PTH) con relación a los ingresos de los productores no participantes del Proyecto o Población No Meta (PNM). Este comportamiento refleja que los participantes del PTH han logrado mejorías sustanciales en la disponibilidad del recurso económico así como la creación de condiciones básicas para mejorar sus condiciones de vida. Además los procesos económicos dan lugar a una diferenciación económica entre los pobladores de la zona, pero por otro lado, establece un grado de interés y motivación para Integrarse de una manera activa como participantes del proyecto. En lo que se refiere a capacitación, se estima un 139% de sobrecumplimiento, según la planificación de eventos de capacitación, sobre todo en los años 1993 y 1994. Es importante destacar que este sobrecumplimiento de las capacitaciones tienen un producto y se refleja con la aplicación de las actividades del tipo agroforestal por parte de los participantes del proyecto y con la concepción creada en éstos sobre la preservación de los recursos naturales- Otro elemento Importante que pone de manifiesto el producto de las capacitaciones es el haber desarrollado capacidades en un buen grupo de productores estimados en 60 como futuros promotores de acciones de desarrollo. Por otro lado, han sido diversos los factores que determinaron una disminución en los rendimientos de los principales cultivos (maíz y frijol) entre ellos las variaciones climáticas y el mal manejo, sobre todo en la época de Apante de los productores de la PM con relación a los productores de la PNM. En el rubro Maíz los rendimientos del año 1995 disminuyeron en un 31% con relación a los del año de 1993, contrario a los rendimientos de la PNM que se incrementaron en un 2.1%. En el rubro frijol durante el mismo período, en las dos poblaciones en estudio, se redujo en un 35 y 34 % para la PM y la PNM respectivamente. Sin embargo, la tendencia de este comportamiento es revertirse, ya que los productores de la PNM realizan aplicaciones de agroquímicos para poder obtener estos resultados y los de la PM utilizan prácticas de Conservación de Suelo que a un corto plazo se reflejarán en un incremento de los rendimientos. El rubro pecuario mostró un comportamiento relativamente bajo con relación a los índices zootécnicos previstos, encontrándose mejores resultados en la PNM. Esto se atribuye fundamentalmente a la poca incidencia de las acciones que ha tenido el proyecto hacia este rubro justificado por el alto costo de Inversión que requiere tanto en material biológico como en Infraestructura. En las especies menores (cerdos y aves) no existen indicadores en los registros productivos ni en los resultados esperados por el proyecto. Esto puede valorarse como negativo y como debilidad manifiesta en el proceso de definición para la ampliación de las acciones del proyecto, de manera que no permite cuantificar ni cualificar el comportamiento de éstas ni el Impacto que pueden generar en los sistemas productivos de las unidades de producción. De tal manera que referirnos promedios de 2.66 cerdos por productor (de 13 productores), a diferencia de la PNM que 9 productores reportan un promedio de 1.33 unidades, a esto se agrega que ambas poblaciones reportan el suministro del mismo tipo de alimento (maíz, yuca, guineo, suero y sal). En aves se reportan productores de la PM con mayor número con relación a los de la PNM, con un promedio de 17 y 13 respectivamente. La alimentación suministrada por parte de la PM, se basa fundamentalmente en maíz y concentrados caseros (técnica promovida por el proyecto), este manejo aplicado a las aves por la PM tiene como resultado un aumento en la disponibilidad de alimento para la dieta familiar haciendo uso de los recursos locales de la unidad de producción, sucediendo lo contrario en los productores de la PNM, que para alimentar a las aves por lo general se destina el grano de maíz, compitiendo de esta manera, aves y familia por el alimento. Referente a la diversificación de la producción en la PM1 existe un fuerte predominio (del 32%) de 6 rubros establecidos en la finca y hay una tendencia (de un 21%) a incrementarse hasta 8 rubros como lo manifiestan las metas propuestas por el proyecto inicial. Un elemento importante que explica estos comportamientos la participación activa del personal técnico con los participantes del proyecto, ya que se establecen en un proceso de acción-reflexión-acción. Sucede lo contrario con los productores del grupo de la PNM que siendo 5 los rubros que mayor predominan en las fincas y con poca tendenda (16%) a incrementarse hasta 7 rubros por finca. En lo que adopción de tecnología se refiere, se manifiesta un número de productores (PM) que han adoptado de 3-4 prácticas por año y ha ido en aumento a lo largo de los tres años, desde el 11% en 1993 al 30% en 1995, y se establecen en los rubros de Maíz, Frijol y café. Mucho ha influido y de manera positiva en este proceso de adopción los niveles de comunicación desarrollados por los técnicos con los participantes del proyecto, sin embargo han sido diversos los factores que han influido de manera negativa en el proceso los cuales se reflejaron como: los resultados de las técnicas no son a corto plazo; hay mucha inversión de mano de obra; se hace uso de Insumas externos; hay una resistencia al uso de las tecnologías. La participación de la mujer de la PM en las actividades del proyecto es muy marcado, 124 jornales/año contra 62 jornales de la PNM, fundamentalmente en las actividades de carácter agropecuario, lo cual refleja una clara influencia del PTH en las mujeres de la comarca. A esto se le agrega el involucramiento en un 81% de las mujeres en al menos, un evento de capacitación del PTH a lo largo de tres años. Una evidencia de la diferencia en el comportamiento de las mujeres participantes en el Proyecto o PM es que al aplicar el Instrumento individual se evidencio una mayor fluidez, menor temor de expresión y un ambiente de mayor confianza, mientras que en la mayoría de las no participantes o PNM, se mostró mayor temor a expresar sus ideas y con muy poca alocución a las preguntas formuladas. La experiencia organizativa en la zona de Influencia del proyecto históricamente ha sido muy negativa, por la gran influencia política en dichas organizaciones. El proyecto influyó de una manera muy positiva en el aspecto de la organizacion campesina/ debido a la dinámica neutral de trabajo y en fundón de un bien colectivo, como es la preservación de los recursos naturales. Esto hace posible que en dinámicas de capacitación, surjan expresiones de participantes del proyecto sobre el beneficio de la organización, tales como "El pecado no está en la organización en sí, si no en la forma en cómo es concebida y coordinada"; es importante destacar que estas concepciones de los participantes, dan pautas para la valoración de que se han establecido las bases para desarrollar de una manera más efectiva las acciones impulsadas con un carácter sostenible. Considerando que los resultados obtenidos en el estudio muestran mejoras considerables y sustanciales en los aspectos socioeconómicos de las familias campesinas participantes del proyecto, es importante implementar una tercera fase de ejecución, de manera que se logre fortalecer y ampliar los componentes del proyecto, tomando en cuenta en la planificación una dotación de recursos humanos y económicos para garantizar la influencia a otras zonas aledañas a Pancasan.