Neuroscience
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Despite the debilitating consequences and the widespread prevalence of brain trauma insults including spinal cord injury (SCI) and traumatic brain injury (TBI), there are currently few effective therapies for most of brain trauma sequelae. As a consequence, there has been a major quest for identifying better diagnostic tools, predictive models, and directed neurotherapeutic strategies in assessing brain trauma. Among the hallmark features of brain injury pathology is the central nervous systems' (CNS) abnormal activation of the immune response post-injury. ⋯ It is being suggested that there may be an analogy of CNS autoantibodies secretion with the pathophysiology of autoimmune diseases, in which case, understanding and defining the role of autoantibodies in brain injury paradigm (SCI and TBI) may provide a realistic prospect for the development of effective neurotherapy. In this work, we will discuss the accumulating evidence about the appearance of autoantibodies following brain injury insults. Furthermore, we will provide perspectives on their potential roles as pathological components and as candidate markers for detecting and assessing CNS injury.
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Work from the past 40years has unraveled a wealth of information on the cellular and molecular mechanisms underlying synaptic plasticity and their relevance in physiological brain function. At the same time, it has been recognized that a broad range of neurological diseases may be accompanied by severe alterations in synaptic plasticity, i.e., 'maladaptive synaptic plasticity', which could initiate and sustain the remodeling of neuronal networks under pathological conditions. ⋯ This review focuses on recent experimental evidence, which highlights the fundamental role of endoplasmic reticulum-mediated Ca(2+) signals in modulating the duration, direction, extent and type of synaptic plasticity. We discuss the possibility that intracellular Ca(2+) stores may regulate synaptic plasticity and hence behavioral and cognitive functions at the interface between physiology and pathology.
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In Parkinson's disease (PD), elevated beta (15-35Hz) power in subcortical motor networks is widely believed to promote aspects of PD symptomatology, moreover, a reduction in beta power and coherence accompanies symptomatic improvement following effective treatment with l-DOPA. Previous studies have reported symptomatic improvements that correlate with changes in cortical network activity following GABAA receptor modulation. In this study we have used whole-head magnetoencephalography to characterize neuronal network activity, at rest and during visually cued finger abductions, in unilaterally symptomatic PD and age-matched control participants. ⋯ However, the absolute level of movement-related beta desynchronization was not altered. These results show that low-dose zolpidem not only reduces contralateral beta but also increases ipsilateral beta, while rebalancing the dynamic range of M1 network oscillations between the two hemispheres. These changes appear to underlie the symptomatic improvements afforded by low-dose zolpidem.
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Neuropathy target esterase (NTE) is a protein involved in the development of a polyneuropathy caused by exposure to certain organophosphorus compounds. In vivo and in vitro studies have also associated NTE with embryonic development since NTE null mice embryos are non-viable, and silencing the NTE-codifying gene (Pnpla6) in mouse embryonic stem cells strongly alters the differentiation of vascular and nervous systems. In this paper, human embryonal carcinoma stem cells human-derived NTera2/D1 (hNT2) are used as an in vitro neurodifferentiation model to determine whether PNPLA6 silencing is able to alter the differentiation process. ⋯ Microarray data analysis of the PNPLA6-silenced cells showed alterations in several developmental processes, mainly neurogenesis and epithelium tube morphogenesis. PNPLA6 silencing also led to a reduction in electrical activity and an altered neuronal phenotype. This work is the first proof supporting the hypothesis that NTE plays a role in human early neurodevelopment using a human cell differentiation model.
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The C-terminal fragments-25(CTF25) of TDP-43 is a fragment of TAR DNA-binding protein 43kDa (TDP-43), which is involved in RNA metabolism, neurite outgrowth, and neuronal development and stress granules. Not until recently did evidence suggest that CTF25 might play an important role in amyotrophic lateral sclerosis (ALS) pathogenesis. However, mechanical details on CTF25 causing motor neuron degeneration still remain unknown. ⋯ Furthermore, the neurotoxicity of CTF25 of TDP-43 was dependent on proteasome activity. In addition, electron microscopy showed mitochondrial swelling and cristae dilation in cells expressing CTF25 and that CTF25 aggregates were characterized by filamentous bundles and electron dense granular material. In conclusion, the new cellular model mimics classical toxic TDP-43 cellular model and interestingly the toxicity of CTF25 is dependent on the proteasome.