Neuroscience
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The whole-cell patch-clamp technique was used to record current responses to AMPA, N-methyl-d-aspartate (NMDA), muscimol and dibenzoyl-ATP (Bz-ATP) in superficial (reactive/gliotic) substantia gelatinosa (SG) astrocytes and neurons of spinal cord slices kept for different periods of time in organotypic culture. Currents induced by AMPA, NMDA and muscimol confirmed the existence of their specific receptors in 2-week-old neurons; astrocytes cultured for the same period of time responded to AMPA and muscimol, but not to NMDA. AMPA had a larger effect on 2-week-old astrocytes than on the 1-week-old ones, in spite of a similar sensitivity of the age-matched neurons to this amino acid. ⋯ Neurons located in deep layers exhibited after 1week of culturing much larger Bz-ATP currents than the superficial ones of the same age. In conclusion, whereas resting astrocytes had culture period-independent P2X7 receptor-sensitivity, reactive/gliotic astrocytes exhibited P2X7 receptor-sensitivity increasing in parallel with the prolongation of the time spent in culture. The results with Bz-ATP agree with the facilitation of AMPA-induced currents in reactive astrocytes during development, and with the hypothesis that extracellular ATP is an ontogenetically early transmitter/signaling molecule in the CNS.
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Neuropathic pain is absent in infants and emergent years after injury. Adult spinal cord microglia play a key role in initiating neuropathic pain, and modulation of microglia is a potential target for treating neuropathic pain. In this study, we evaluated the role of microglia after infant peripheral nerve injury and the effect of exercise on the delayed-onset neuropathic pain. ⋯ Exercise shifted spinal cord microglia polarization to the M2 phenotype and reduced neuropathic pain. In addition, IL-10 increased and TNF-α decreased after exercise, and intrathecal injection of the IL-10 antibody reduced the exercise-induced analgesia. Our study found that infant nerve injury induced delayed spinal cord microglia polarization to the M1 phenotype and that exercise was effective in the treatment of delayed adolescent neuropathic pain via the modulation of microglial polarization.
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Fragile X mental retardation protein (FMRP), an important RNA-binding protein responsible for fragile X syndrome, is involved in posttranscriptional control of gene expression that links with brain development and synaptic functions. Here, we reveal a novel role of FMRP in pre-mRNA alternative splicing, a general event of posttranscriptional regulation. Using co-immunoprecipitation and immunofluorescence assays, we identified that FMRP interacts with an alternative-splicing-associated protein RNA-binding protein 14 (RBM14) in a RNA-dependent fashion, and the two proteins partially colocalize in the nuclei of hippocampal neurons. ⋯ RNA immunoprecipitation assays indicate that FMRP promotes RBM14's binding to the mRNA targets. In addition, overexpression of the long form of Protrudin or the short form of Tau promotes protrusion growth of the retinoic acid-treated, neuronal-differentiated Neuro-2a cells. Together, these data suggest a novel function of FMRP in the regulation of pre-mRNA alternative splicing through RBM14 that may be associated with normal brain function and FMRP-related neurological disorders.
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Pain is processed in a large neural network that partially overlaps structures involved in emotion processing. Despite the fact that pain and emotion are known to share neural regions and interact in numerous clinical conditions, relatively little is known about the interaction of pain and emotion at the neural level. This study on healthy adults aimed to investigate the interaction between negative and positive emotional stimuli and experimental pain in an essential pain processing network. ⋯ The interaction of positive emotion and pain stimuli led to bilateral activation of the SII and left insula. These findings reveal interaction in parts of the pain processing network during simultaneous emotion and physical pain. We demonstrated a valence-independent interaction of emotion and pain in SII.
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Detection of awareness in patients with consciousness disorders is a challenge that can be facilitated by functional neuroimaging. We elaborated a functional magnetic resonance imaging (fMRI) protocol to detect covert activity in altered states of consciousness. We hypothesized that passive listening to narratives with graduated emotional charge triggers graduated cerebral activations. ⋯ The protocol proved efficient at triggering graduated cerebral activations: low emotional charge, superior temporal gyri and sulci; mean emotional charge, same as low emotional charge plus bilateral premotor cortices and left inferior frontal gyrus; high emotional charge, cingulate, temporal, frontal, prefrontal and angular areas, thalamus and cerebellum. Semantic autobiographical memory revealed larger activations than episodic autobiographical memory. Independent ROI analysis confirmed the preponderant contribution of narratives with autobiographical memory content in triggering cerebral activation, not only in autobiographical memory-sensitive areas, but also in voice-sensitive, language-sensitive and semantic memory-sensitive areas.