Experimental neurology
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Daily rhythms in neural activity underlie circadian rhythms in sleep-wake and other daily behaviors. The cells within the mammalian suprachiasmatic nucleus (SCN) are intrinsically capable of 24-h timekeeping. ⋯ Recent studies have identified a small number of neuropeptides critical for this ability to synchronize and sustain coordinated daily rhythms. This review highlights the roles of specific intracellular and intercellular signals within the SCN that underlie circadian synchrony.
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Severed axons in adult mammals do not regenerate appreciably after central nervous system (CNS) injury due to developmentally determined reductions in neuron-intrinsic growth capacity and extracellular environment for axon elongation. Chondroitin sulfate proteoglycans (CSPGs), which are generated by reactive scar tissues, are particularly potent contributors to the growth-limiting environment in mature CNS. Thus, surmounting the strong inhibition by CSPG-rich scar is an important therapeutic goal for achieving functional recovery after CNS injuries. ⋯ CSPGs also may act by binding to two receptors for myelin-associated growth inhibitors, Nogo receptors 1 and 3 (NgR1 and NgR3). If confirmed, it would suggest that CSPGs have multiple mechanisms by which they inhibit axon growth, making them especially potent and difficult therapeutic targets. Identification of CSPG receptors is not only important for understanding the scar-mediated growth suppression, but also for developing novel and selective therapies to promote axon sprouting and/or regeneration after CNS injuries, including spinal cord injury (SCI).
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Experimental neurology · Jun 2012
ReviewRole of noncoding RNAs in trinucleotide repeat neurodegenerative disorders.
Increasingly complex networks of noncoding RNAs are being found to play important and diverse roles in the regulation of gene expression throughout the genome. Many lines of evidence are linking mutations and dysregulations of noncoding RNAs to a host of human diseases, and noncoding RNAs have been implicated in the molecular pathogenesis of some neurodegenerative disorders. The expansion of trinucleotide repeats is now recognized as a major cause of neurological disorders. Here we will review our current knowledge of the proposed mechanisms behind the involvement of noncoding RNAs in the molecular pathogenesis of neurodegenerative disorders, particularly the sequestration of specific RNA-binding proteins, the regulation of antisense transcripts, and the role of the microRNA pathway in the context of known neurodegenerative disorders caused by the expansion of trinucleotide repeats.
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Experimental neurology · May 2012
ReviewCell-based transplantation strategies to promote plasticity following spinal cord injury.
Cell transplantation therapy holds potential for repair and functional plasticity following spinal cord injury (SCI). Stem and progenitor cells are capable of modifying the lesion environment, providing structural support and myelination and increasing neurotrophic factors for neuroprotection and endogenous activation. Through these effects, transplanted cells induce plasticity in the injured spinal cord by promoting axonal elongation and collateral sprouting, remyelination, synapse formation and reduced retrograde axonal degeneration. ⋯ Hence, combinatorial stem cell transplantation strategies which could potentially directly address tissue sparing and neuroplasticity in chronic SCI show promise. Rigorous evaluation of combinatorial approaches using stem cell transplantation with appropriate preclinical animal models of SCI is needed to advance therapeutic strategies to the point where clinical trials are appropriate. Given the high patient demand for and clinical trial precedent of cell transplantation therapy, combination stem cell therapies have the promise to provide improved quality of life for individuals, with corresponding socioeconomic benefit.
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Experimental neurology · May 2012
ReviewCortical and subcortical compensatory mechanisms after spinal cord injury in monkeys.
This is a review of our investigations into the neuronal mechanisms of functional recovery after spinal cord injury (SCI) in a non-human primate model. In primates, the lateral corticospinal tract (l-CST) makes monosynaptic connections with spinal motoneurons. The existence of direct cortico-motoneuronal (CM) connections has been thought to be the basis of dexterous digit movements, such as precision gripping. ⋯ Such changes in cortical activity in M1 and PMv have been shown to accompany changes in the expressions of plasticity-related genes, such as GAP-43. Changes in the dynamic properties of neural circuits, both at the cortical and subcortical levels, are time-dependent. Multidisciplinary studies to clarify how the changes in the dynamic properties of individual components of the large-scaled networks are coordinated during recovery will help to develop effective therapeutic strategies to recovery from SCI.