Neuroscience
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Mesenchymal stem cells (MSCs) obtained from bone marrow (BM) have been shown to promote neuronal growth and survival. However, the comparative effects of MSCs of different sources, including menstrual MSCs (MenSCs), BM, umbilical cord and chorion stem cells on neurite outgrowth have not yet been explored. Moreover, the modulatory effects of MSCs may be mediated by paracrine mechanisms, i.e. by molecules contained in the MSC secretome that includes soluble factors and extracellular vesicles such as microvesicles and/or exosomes. ⋯ The extracellular vesicle fractions showed a distinctive effect: while the exosome-enriched fraction enhanced neurite outgrowth, the microvesicle-enriched fraction displayed an inhibitory effect. When we compared exosome fractions of different human MSC sources, MenSC exosomes showed superior effects on the growth of the longest neurite in cortical neurons and had a comparable effect to BM-SC exosomes on neurite outgrowth in dorsal root ganglia neurons. Thus, the growth-stimulating effects of exosomes derived from MenSCs as well as the opposing effects of both extracellular vesicle fractions provide important information regarding the potential use of MenSCs as therapeutic conveyors in neurodegenerative pathologies.
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Transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) exhibit considerable trial-to-trial variability, potentially reducing the sensitivity and reproducibility of this measure. While increasing the number of trials will improve accuracy, prolonged recording blocks are not always feasible. In this study, we investigated the minimum number of trials required to provide a measure of human corticospinal excitability that is stable both within and between sessions. ⋯ Extending the number of trials beyond 30 provided no additional benefit. Collecting 30 trials may be optimal for reliably estimating corticospinal excitability using TMS. These findings may have significant implications for using TMS to measure corticospinal excitability in both basic and clinical research settings.
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The choroid plexus (CP) located in brain ventricles, by forming the interface between the blood and the cerebrospinal fluid (CSF) is in a privileged position to monitor the composition of these body fluids. Yet, the mechanisms involved in this surveillance system remain to be identified. The taste transduction pathway senses some types of molecules, thereby evaluating the chemical content of fluids, not only in the oral cavity but also in other tissues throughout the body, such as some cell types of the airways, the gastrointestinal tract, testis and skin. ⋯ This effect was diminished in the presence of the bitter receptor blocker Probenecid. In summary, we described the expression of the taste-related components involved in the transduction signaling cascade in CP. Taken together, our results suggest that the taste transduction pathway in CPEC makes use of T2R receptors in the chemical surveillance of the CSF composition, in particular to sense bitter noxious compounds.
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Although thrombin has an important role in both central and peripheral nerve diseases, characterization of the anatomical distribution of its proteolytic activity has been limited by available methods. This study presents the development, challenges, validation and implementation of a novel histochemical method for visualization of thrombin activity in the nervous system. The method is based on the cleavage of the substrate, Boc-Asp(OBzl)-Pro-Arg-4MβNA by thrombin to liberate free 4-methoxy-2-naphthylamine (4MβNA). ⋯ In addition, 24 h following crush injury, focal areas of highly elevated thrombin activity were detected in teased sciatic fibers. This observation was supported by the biochemical assay and western blot technique. The histochemical method developed in this study can serve as an important tool for studying the role of thrombin in physiological and pathological conditions.
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Postoperative cognitive dysfunction (POCD) is an important complication following major surgery and general anesthesia in older patients. However, the etiology of POCD remains largely to be determined. It is unknown how surgical stress and psychological stress affect the postoperative learning and memory function in geriatric patients. ⋯ Analysis of brain tissue revealed a significant involvement of the AKT/mTOR pathway in the impairment of cognition. These data suggested that surgical stress could induce cognitive impairment in aged mice and perioperative psychological stress is not a constitutive factor of POCD. The AKT/mTOR pathway is likely involved as one of the underlying mechanisms of the development of POCD.