Neuroscience
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Strength training of one limb results in a substantial increase in the strength of the untrained limb, however, it remains unknown what the corticospinal responses are following either eccentric or concentric strength training and how this relates to the cross-education of strength. The aim of this study was to determine if eccentric or concentric unilateral strength training differentially modulates corticospinal excitability, inhibition and the cross-transfer of strength. ⋯ The results show that eccentric training uniquely modulates corticospinal excitability and inhibition of the untrained limb to a greater extent than concentric training. These findings suggest that unilateral eccentric contractions provide a greater stimulus in cross-education paradigms and should be an integral part of the rehabilitative process following unilateral injury to maximize the response.
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Astrocytes are major supportive cells in brains with important functions including providing nutrients and regulating neuronal activities. In this study, we demonstrated that astrocytes regulate amyloid precursor protein (APP) processing in neuronal cells through secretion of group IIA secretory phospholipase A2 (sPLA2-IIA). When astrocytic cells (DITNC) were mildly stimulated with the pro-inflammatory cytokines, such as TNF α and IL-1β, sPLA2-IIA was secreted into the medium. ⋯ These changes were abrogated by KH064, a selective inhibitor of sPLA2-IIA. In addition, exposing SH-SY5Y cells to recombinant human sPLA2-IIA also increased membrane fluidity, accumulation of APP at the cell surface, and secretion of sAPPα, but without altering total expressions of APP, α-secretases and β-site APP cleaving enzyme (BACE1). Taken together, our results provide novel information regarding a functional role of sPLA2-IIA in astrocytes for regulating APP processing in neuronal cells.
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The presence of mRNAs in synaptic terminals and their regulated translation are important factors in neuronal communication and plasticity. Heterogeneous nuclear ribonucleoprotein (hnRNP) complexes are involved in the translocation, stability, and subcellular localization of mRNA and the regulation of its translation. Defects in these processes and mutations in components of the hnRNP complexes have been related to the formation of cytoplasmic inclusion bodies and neurodegenerative diseases. ⋯ In this report we present further biochemical and molecular characterization that shows endogenous p65 to be an SDS-stable dimer composed of ∼37-kDa hnRNPA/B-like subunits. We cloned and expressed a recombinant protein corresponding to squid hnRNPA/B-like protein and showed its propensity to aggregate and form SDS-stable dimers in vitro. Our data suggest that this unique hnRNPA/B-like protein co-localizes with synaptic vesicle protein 2 and RNA-binding protein ELAV and thus may serve as a link between local mRNA processing and presynaptic function and regulation.
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Inflammatory response induced by protrused nucleus pulposus (NP) has been shown to play a crucial role in the process of radicular pain. Lipoxins represent a unique class of lipid mediators that have anti-inflammatory and pro-resolving action. The present study was undertaken to investigate if intrathecal lipoxin A4 (LXA4) could alleviate mechanical allodynia in the rat models of application of NP to the L5 dorsal root ganglion (DRG). ⋯ Intrathecal injection of LXA4 alleviated the development of neuropathic pain, inhibited the upregulation of pro-inflammatory cytokines (TNF-α and IL-1β), upregulated the expression of anti-inflammatory cytokines (TGF-β1 and IL-10) and attenuated the activation of NF-κB/p65, p-ERK, p-JNK, but not p-p38, in a dose-dependent manner. In this study, we have demonstrated that LXA4 potently alleviate radicular pain in a rat model of non-compressive lumbar disc herniation. The anti-inflammatory and pro-resolution properties of LXA4 have shown a great promise for the management of radicular pain caused by intervertebral disc herniation.
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Activation of peroxisome proliferator-activated receptors (PPARs), namely PPARγ and PPARδ, has been shown to provide neuroprotection in a number of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease (PD). The observed neuroprotective effects in experimental models of PD have been linked to anti-oxidant and anti-inflammatory actions. This study aimed to analyze the full influence of these receptors in neuroprotection by generating a nerve cell-specific conditional knock-out of these receptors and subjecting these genetically modified mice to the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to model dopaminergic degeneration. ⋯ Presence of one or both these receptors show a trend toward protection against this degeneration, as higher dopaminergic cell immunoreactivity and striatal monoamine levels are evident. These data supplement recent studies that have elected to use agonists of the receptors to regulate immune responses. The results place further importance on the activation of PPARs and the neuroprotective roles these have in inflammatory processes linked to neurodegenerative processes.