Neuroscience
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The functional differentiation between regions of psoas major (PM) and quadratus lumborum (QL) may underlie a mechanical basis for recruitment of motor units across the muscle. These mechanically unique fascicle regions of these complex multifascicular muscles, PM and QL, are likely to be controlled independently by the central nervous system (CNS). Fine-wire electrodes recorded the electromyographic activity of the PM fascicles arising from the transverse process (PM-t) and vertebral body (PM-v) and the anterior (QL-a) and posterior (QL-p) layers of QL on the right side during a postural perturbation associated with rapid arm movements. ⋯ The spatial and temporal features of discrete activity of different regions within PM and QL matched their differing mechanical advantage predicted from their anatomy. These findings suggest that the CNS differentially activates individual regions within complex spine muscles to control the three-dimensional forces applied to the spine. The data also point to a sophisticated control of muscle activation that appears based on mechanical advantage.
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It is important to clarify the neural mechanisms underlying fatigue sensation. There have been several studies which identified brain regions in which the level of the neural activities was correlated with the subjective level of fatigue. However, the neural activity evoked when we evaluate our level of fatigue may not be related to the subjective level of fatigue. ⋯ The proportion of participants in whom ECDs were observed in the PCC in the evaluation session was significantly higher than that in the control session (McNemar test). In addition, the intensities of the ECDs were positively associated with the extent to which the participants successfully evaluated the fatigue in their right hand in the evaluation session. These data suggest that the PCC is involved in the neural substrates associated with self-evaluation of physical fatigue.
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Precise regulation of the chloride homeostasis crucially determines the action of inhibitory transmitters GABA and glycine and thereby endows neurons or even discrete neuronal compartments with distinct physiological responses to the same transmitters. In mammals, the signaling mediated by GABAA/glycine receptors shifts during early postnatal life from depolarization to hyperpolarization, due to delayed maturation of the chloride homeostasis system. While the activity of the secondary active, K(+)-Cl(-)-extruding cotransporter KCC2, renders GABA/glycine hyperpolarizing in auditory brainstem nuclei of altricial rodents, the mechanisms contributing to the initially depolarizing transmembrane gradient for Cl(-) in respective neurons remained unknown. ⋯ Our data identify the 1Na(+):1K(+):2Cl(-) cotransporter 1 (NKCC1) as the major Cl(-)-loader responsible for depolarizing action of GABA/glycine at postnatal days 3-5 (P3-5). Extracellular GABA/muscimol elicited calcium signaling through R-, L-, and T-type channels, which was dependent on bumetanide- and [Na(+)]e-sensitive Cl(-) accumulation. The "adult like", low intracellular Cl(-) concentration is established during the second postnatal week, through a mechanism engaging the NKCC1-down regulation between P5 and P15 and ongoing KCC2-mediated Cl(-)-extrusion.
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Eugenol is a bioactive plant extract used as an analgesic agent in dentistry. The structural similarity of eugenol to cinnamaldehyde, an active ligand for transient receptor potential ankyrin 1 (TRPA1), suggests that eugenol might produce its effect via TRPA1, in addition to TRPV1 as we reported previously. In this study, we investigated the effect of eugenol on TRPA1, by fura-2-based calcium imaging and patch clamp recording in trigeminal ganglion neurons and in a heterologous expression system. ⋯ In addition, eugenol response was observed in trigeminal ganglion neurons from TRPV1 knockout mice and human embryonic kidney 293 cell lines that express human TRPA1, which was inhibited by TRPA1-specific antagonist HC-030031. Eugenol-evoked TRPA1 single channel activity and eugenol-induced TRPA1 currents were dose-dependent with EC50 of 261.5μM. In summary, these results demonstrate that the activation of TRPA1 might account for another molecular mechanism underlying the pharmacological action of eugenol.
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The amyloid precursor protein (APP) and amyloid-β (Aβ) peptide play central roles in the pathology and etiology of Alzheimer's disease. Amyloid-induced impairments in neurogenesis have been investigated in several transgenic mouse models but the mechanism of action remains to be conclusively demonstrated. The changes in neurogenesis during this transition of increasing Aβ levels and plaque formation were investigated in the present study. ⋯ In addition, a unique observation was made using isolated neuroprogenitor cells from TgCRND8 mice which were found to be less viable in culture and produced substantial amounts of secreted Aβ peptides. This suggests that the proliferation of neural progenitors in vivo may be modulated by high levels of APP expression and the resulting Aβ generated directly by the progenitor cells. These findings indicate that cell proliferation is increased prior to Aβ deposition and that cell viability is decreased in TgCRND8 mice over time.