RESUMEN
Flexible cognitive functions, such as working memory (WM), usually require a balance between localized and distributed information processing. However, it is challenging to uncover how local and distributed processing specifically contributes to task-induced activity in a region. Although the recently proposed activity flow mapping approach revealed the relative contribution of distributed processing, few studies have explored the adaptive and plastic changes that underlie cognitive manipulation. In this study, we recruited 51 healthy volunteers (31 females) and investigated how the activity flow and brain activation of the frontoparietal systems was modulated by WM load and training. While the activation of both executive control network (ECN) and dorsal attention network (DAN) increased linearly with memory load at baseline, the relative contribution of distributed processing showed a linear response only in the DAN, which was prominently attributed to within-network activity flow. Importantly, adaptive training selectively induced an increase in the relative contribution of distributed processing in the ECN and also a linear response to memory load, which were predominantly due to between-network activity flow. Furthermore, we demonstrated a causal effect of activity flow prediction through training manipulation on connectivity and activity. In contrast with classic brain activation estimation, our findings suggest that the relative contribution of distributed processing revealed by activity flow prediction provides unique insights into neural processing of frontoparietal systems under the manipulation of cognitive load and training. This study offers a new methodological framework for exploring information integration versus segregation underlying cognitive processing.
Asunto(s)
Función Ejecutiva , Imagen por Resonancia Magnética , Memoria a Corto Plazo , Humanos , Femenino , Masculino , Adulto Joven , Adulto , Memoria a Corto Plazo/fisiología , Función Ejecutiva/fisiología , Mapeo Encefálico , Atención/fisiología , Cognición/fisiología , Encéfalo/fisiología , Red Nerviosa/fisiología , Red Nerviosa/diagnóstico por imagen , Lóbulo Parietal/fisiologíaRESUMEN
Acrylamide (ACR) is a potent toxin that affects the human nervous system. However, the underlying mechanism of ACR neurotoxicity remains poorly understood. In the present study, we investigated whether ACR induces mitochondrion-dependent apoptosis and the involved signaling pathways in PC12 cells. ACR exposure activated the mitochondrial apoptotic pathway in PC12 cells and triggered the up-regulation of Bax/Bcl-2 ratio, excessive release of cytochrome c, cleavage of capase-9 and caspase-3, depolarization of the mitochondrial membrane, structural damages to the mitochondria, and compaction of nuclear heterochromatin. ACR-induced oxidative stress was also observed based on distinct increase in cellular reactive oxygen species (ROS) and malondialdehyde (MDA), and significant decrease in glutathione (GSH). Mitogen-activated protein kinases (MAPK) signaling including extracellular signal-regulated protein kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 were phosphorylated by ROS overproduction in PC12 cells in a time-and dose-dependent manner. ACR promoted the translocation of nuclear factor E2-related factor 2 (Nrf2) from the cytosol to the nucleus, thereby enhancing the expression of downstream γ-glutamyl-cysteine synthetase (γ-GCS). The regulation of Nrf2 activation by MAPK pathways was confirmed by the blockade of MAPK pathways. The suppression of JNK and p38 pathways showed a protective effect on ACR-induced mitochondrial dysfunction and apoptosis. Nrf2 knockdown further enhanced MDA production and reduced GSH generation induced by ACR. These results suggest that MAPK and Nrf2 signaling pathways contribute to mitochondrion-mediated apoptosis induced by ACR in PC12 cells.
Asunto(s)
Acrilamida/toxicidad , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Mitocondrias/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Silenciador del Gen , Glutatión/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Malondialdehído/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/ultraestructura , Factor 2 Relacionado con NF-E2/genética , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Transporte de Proteínas/efectos de los fármacos , Ratas , Transcripción Genética/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Trimethyltin chloride (TMT) is a classic neurotoxicant that can cause severe neurodegenerative diseases. Some signaling pathways involving cell death play pivotal roles in the central nervous system. In this study, the role of Sonic Hedgehog (Shh) and PI3K/Akt pathways in TMT-induced apoptosis and protective effect of Lycium barbarum polysaccharides (LBP) on mouse neuro-2a (N2a) cells were investigated. Results showed that TMT treatment significantly enhanced apoptosis, upregulated proapoptotic Bax, downregulated antiapoptotic Bcl-2 expression, and increased caspase-3 activity in a dose-dependent manner in N2a cells. TMT induced oxidative stress in cells, performing reactive oxygen species (ROS) and malondialdehyde (MDA) excessive generation, and superoxide dismutase (SOD) activity reduction. TMT significantly decreased phosphorylated glycogen synthase kinase-3ß (GSK-3ß) and inhibited Shh and PI3K/Akt pathways. However, the addition of LBP upregulated GSK-3ß phosphorylation, activated Shh and PI3K/Akt pathways, and eventually reduced apoptosis and oxidative stress caused by TMT. The interaction between Shh and PI3K/Akt pathways was clarified by specific PI3K inhibitor LY294002 or Shh inhibitor GDC-0449. Moreover, LY294002 and GDC-0449 pretreatment both induced phosphorylated GSK-3ß downregulation and significantly promoted apoptosis induced by TMT. These results suggest that LBP could reduce TMT-induced N2a cells apoptosis by regulating GSK-3ß phosphorylation, Shh, and PI3K/Akt signaling pathways.
Asunto(s)
Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Transducción de Señal/efectos de los fármacos , Compuestos de Trimetilestaño/toxicidad , Anilidas/farmacología , Animales , Caspasa 3/metabolismo , Línea Celular , Cromonas/farmacología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteínas Hedgehog/antagonistas & inhibidores , Proteínas Hedgehog/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Ratones , Microscopía Fluorescente , Morfolinas/farmacología , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Piridinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/análisis , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Elevated CO(2) may reduce the tolerance of Nilaparvata lugen (N. lugens) to adverse environmental factors through the biological and physiological degeneration of N. lugens. In an artificial climate box, under 375 and 750 µL L(-1) CO(2) levels, the rice stems nutrient content, the nutrient content and enzyme activities of N. lugens nymph fed on rice seedlings exposed to ambient and elevated CO(2) were studied. The results showed that rice stems had significantly higher protein and total amino acid levels under ambient than elevated CO(2) levels. Nymphs had significantly higher protein levels in the ambient CO(2) treatment, while their glucose levels were significantly lower under ambient CO(2) conditions. Significantly higher trypsin activity was observed in nymphs grown in elevated CO(2). Significantly lower activities of the protective enzymes total superoxide dismutase and catalase were observed in the nymphs under ambient CO(2). Meanwhile, the activity of the detoxification enzyme glutathione S-transferase was significantly higher in the ambient CO(2) treatment. Measuring how energy and resources were allocated to enzymes in N. lugens nymphs under elevated CO(2) conditions can provide a more meaningful evaluation of their metabolic tolerances to adverse climatic conditions.