Sustained expression of PGC-1α in the rat nigrostriatal system selectively impairs dopaminergic function

Mitochondrial dysfunction and oxidative stress have been implicated in the etiology of Parkinson's disease. Therefore, pathways controlling mitochondrial activity rapidly emerge as potential therapeutic targets. Here, we explore the neuronal response to prolonged overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), a transcriptional regulator of mitochondrial function, both in vitro and in vivo. In neuronal primary cultures from the ventral midbrain, PGC-1α induces mitochondrial biogenesis and increases basal respiration. Over time, we observe an increasing proportion of the oxygen consumed by neurons which are dedicated to adenosine triphosphate production. In parallel to enhanced oxidative phosphorylation, PGC-1α progressively leads to a decrease in mitochondrial polarization. In the adult rat nigrostriatal system, adeno-associated virus (AAV)-mediated overexpression of PGC-1α induces the selective loss of dopaminergic markers and increases dopamine (DA) catabolism, leading to a reduction in striatal DA content. In addition, PGC-1α prevents the labeling of nigral neurons following striatal injection of the fluorogold retrograde tracer. When PGC-1α is expressed at higher levels following intranigral AAV injection, it leads to overt degeneration of dopaminergic neurons. Finally, PGC-1α overexpression does not prevent nigrostriatal degeneration in pathologic conditions induced by α-synuclein overexpression. Overall, we find that lasting overexpression of PGC-1α leads to major alterations in the metabolic activity of neuronal cells which dramatically impair dopaminergic function in vivo. These results highlight the central role of PGC-1α in the function and survival of dopaminergic neurons and the critical need for maintaining physiological levels of PGC-1α activit

Extracellular Potassium and Glutamate Interact To Modulate Mitochondria in Astrocytes.

Astrocytes clear glutamate and potassium, both of which are released into the extracellular space during neuronal activity. These processes are intimately linked with energy metabolism. Whereas astrocyte glutamate uptake causes cytosolic and mitochondrial acidification, extracellular potassium induces bicarbonate-dependent cellular alkalinization. This study aimed at quantifying the combined impact of glutamate and extracellular potassium on mitochondrial parameters of primary cultured astrocytes. Glutamate in 3 mM potassium caused a stronger acidification of mitochondria compared to cytosol. 15 mM potassium caused alkalinization that was stronger in the cytosol than in mitochondria. While the combined application of 15 mM potassium and glutamate led to a marked cytosolic alkalinization, pH only marginally increased in mitochondria. Thus, potassium and glutamate effects cannot be arithmetically summed, which also applies to their effects on mitochondrial potential and respiration. The data implies that, because of the nonlinear interaction between the effects of potassium and glutamate, astrocytic energy metabolism will be differentially regulated

Mecanismos neurocognitivos de la terapia basada en mindfulness

Presentamos un resumen y una breve historia del creciente campo de Intervenciones Basadas en mindfulness o conciencia plena. En los últimos tiempos, existe un gran interés en este modelo terapéutico para reducir la vulnerabilidad al estrés crónico y distrés emocional. Mindfulness requiere intencionalmente enfocar nuestra atención a las experiencias que ocurren en el momento presente. A medida que la investigación avanza en esta temática, es vital definir cuidadosamente la estructura de mindfulness y comprender mejor sus mecanismos de acción neurocognitiva. Este informe presenta un marco conceptual que enfatiza el papel central de control atencional y mecanismos de sostenibilidad para desarrollar las habilidades de conciencia plena. También, repasamos la estructura de mindfulness y la autorregulación de las emociones; luego describimos brevemente nuestra investigación relacionada con nuestro programa de Reducción del Estrés en Cáncer de Mama basado en Mindfulness (MBSR-AC) en la University of South Florida. Se presenta, a partir de esta premisa, un modelo propuesto que explica nuestros mecanismos cognitivos basados en la lógica del modelo de biocomportamental

Estructura factorial del inventario multicultural de la depresión, estado-rasgo: Rol de las emociones positivas de la depresión

El propósito de este artículo fue presentar la construcción del inventario multicultural de la depresión, estado-rasgo (Imuder).Tomando en consideración el marco teórico de Susan Folkman acerca de la coexistencia de emociones positivas y negativas en el proceso de estrés severo y depresión, se procedió a la elaboración de ítems caracterizando estados y rasgos de emociones que expresan la presencia o ausencia de depresión. En base a una muestra multicultural con participantes de diversos países latinoamericanos, se realizó el análisis factorial de componentes principales con rotaciones promax, a fin de determinar la validez de constructo y la consistencia interna del instrumento

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush.

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous null mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21days in wild-type mice to greater than 38days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4weeks and tibial mixed sensory and motor nerve at 3weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush

The assessment of the perceived emotional distress: The neglected side of cancer care

The purpose of this research was to present the latest development of the The Perceived Emotional Distress Inventory (PEDI) as a brief 15-item self-report measure intended to be used for the assessment of psychological distress in cancer patients. Factor Analyses of Principal Components with promax rotations were performed with a combined male and female sample of 481 cancer patients at St. Joseph’s hospital Cancer Institute in Tampa, Florida, to provide further evidence of construct validity. The factor structure, internal consistency, and Pearson correlation coefficients of the PEDI are presented in this report. The factor analysis identified three factors comparable to those found in previous samples in USA: The first factor, anxiety/depression; second factor, hopelessness; and third factor, anger expression. Global alpha coefficient of 0.92 for the inventory indicates strong internal consistency. Pearson correlations between the subscales of the instrument is impressive for such a brief measure. This study emphasizes the need for a brief, self-report instrument to assess anger expression, anxiety, depression and hopelessness as components of perceived emotional distress in cancer patients, while explicitly excluding the potentially confounding effects of somatic symptoms commonly associated with cancer treatments. Further research will be needed to provide information about the PEDI’s use in populations other than cancer patients including attempts to replicate these findings in more heterogeneous populations

Sustained expression of PGC-1α in the rat nigrostriatal system selectively impairs dopaminergic function

Mitochondrial dysfunction and oxidative stress have been implicated in the etiology of Parkinson's disease. Therefore, pathways controlling mitochondrial activity rapidly emerge as potential therapeutic targets. Here, we explore the neuronal response to prolonged overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), a transcriptional regulator of mitochondrial function, both in vitro and in vivo. In neuronal primary cultures from the ventral midbrain, PGC-1α induces mitochondrial biogenesis and increases basal respiration. Over time, we observe an increasing proportion of the oxygen consumed by neurons which are dedicated to adenosine triphosphate production. In parallel to enhanced oxidative phosphorylation, PGC-1α progressively leads to a decrease in mitochondrial polarization. In the adult rat nigrostriatal system, adeno-associated virus (AAV)-mediated overexpression of PGC-1α induces the selective loss of dopaminergic markers and increases dopamine (DA) catabolism, leading to a reduction in striatal DA content. In addition, PGC-1α prevents the labeling of nigral neurons following striatal injection of the fluorogold retrograde tracer. When PGC-1α is expressed at higher levels following intranigral AAV injection, it leads to overt degeneration of dopaminergic neurons. Finally, PGC-1α overexpression does not prevent nigrostriatal degeneration in pathologic conditions induced by α-synuclein overexpression. Overall, we find that lasting overexpression of PGC-1α leads to major alterations in the metabolic activity of neuronal cells which dramatically impair dopaminergic function in vivo. These results highlight the central role of PGC-1α in the function and survival of dopaminergic neurons and the critical need for maintaining physiological levels of PGC-1α activity

The effects of mindfulness-based stress reduction on objective and subjective sleep parameters in women with breast cancer: a randomized controlled trial

Abstract Objective: The purpose of this study was to investigate the effects of mindfulness-based stress reduction for breast cancer survivors (MBSR(BC)) on multiple measures of objective and subjective sleep parameters among breast cancer survivors (BCS). Methods: Data were collected using a two-armed randomized controlled design among BCS enrolled in either a 6-week MBSR(BC) program or a usual care (UC) group with a 12-week follow-up. The present analysis is a subset of the larger parent trial (ClinicalTrials.gov Identifier: NCT01177124). Seventy-nine BCS participants (mean age 57 years), stages 0-III, were randomly assigned to either the formal (in-class) 6-week MBSR(BC) program or UC. Subjective sleep parameters (SSP) (i.e., sleep diaries and the Pittsburgh Sleep Quality Index (PSQI)) and objective sleep parameters (OSP) (i.e., actigraphy) were measured at baseline, 6 weeks, and 12 weeks after completing the MBSR(BC) or UC program. Results: Results showed indications of a positive effect of MBSR(BC) on OSP at 12 weeks on sleep efficiency (78.2% MBSR(BC) group versus 74.6% UC group, p = 0.04), percent of sleep time (81.0% MBSR(BC) group versus 77.4% UC group, p = 0.02), and less number waking bouts (93.5 in MBSR (BC) group versus 118.6 in the UC group, p < 0.01). Small nonsignificant improvements were found in SSP in the MBSR(BC) group from baseline to 6 weeks (PSQI total score, p = 0.09). No significant relationship was observed between minutes of MBSR(BC) practice and SSP or OSP. Conclusions: These data suggest that MBSR(BC) may be an efficacious treatment to improve objective and subjective sleep parameters in BCS