Molecular and cellular neurosciences
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Mol. Cell. Neurosci. · Apr 2004
Comparative StudyNG2 proteoglycan expression in the peripheral nervous system: upregulation following injury and comparison with CNS lesions.
The chondroitin sulphate proteoglycan NG2 blocks neurite outgrowth in vitro and thus may be able to inhibit axonal regeneration in the CNS. We have used immunohistochemistry to compare the expression of NG2 in the PNS, where axons regenerate, and the spinal cord, where regeneration fails. NG2 is expressed by satellite cells in dorsal root ganglia (DRG) and in the perineurium and endoneurium of intact sciatic nerves of adult rats. ⋯ Compression and partial transection injuries to the spinal cord also caused an upregulation of NG2, and NG2-positive cells and processes invaded the lesion sites. Transganglionically labelled ascending dorsal column fibres, stimulated to sprout by a conditioning sciatic nerve injury, ended in the borders of lesions among many NG2-positive processes. Thus, NG2 upregulation is a feature of the response to injury in peripheral nerves and in the spinal cord, but it does not appear to limit regeneration in the sciatic nerve.
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Mol. Cell. Neurosci. · Feb 2004
Schwann cells and astrocytes induce synapse formation by spinal motor neurons in culture.
Glia constitute 90% of cells in the human nervous system, but relatively little is known about their functions. We have been focusing on the potential synaptic roles of glia in the CNS. We recently found that astrocytes increase the number of mature, functional synapses on retinal ganglion cells (RGCs) by sevenfold and are required for synaptic maintenance in vitro. ⋯ This synapse-promoting activity is not mediated by direct glial-neuronal cell contact but rather is mediated by secreted molecule(s) from the Schwann cells, as we previously found for astrocytes. Interestingly, the synapse-promoting activity from astrocytes and Schwann cells was functionally similar: Schwann cells also promoted synapse formation between retinal ganglion cells, and astrocytes promoted synapse formation between spinal motor neurons. These studies show that both astrocytes and Schwann cells strongly promote synapse formation between spinal motor neurons and demonstrate that glial regulation of synaptogenesis extends to other neuron types.
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Mol. Cell. Neurosci. · Nov 2003
Fibroblast growth factor-2 gene delivery stimulates axon growth by adult retinal ganglion cells after acute optic nerve injury.
Basic fibroblast growth factor (or FGF-2) has been shown to be a potent stimulator of retinal ganglion cell (RGC) axonal growth during development. Here we investigated if FGF-2 upregulation in adult RGCs promoted axon regrowth in vivo after acute optic nerve injury. Recombinant adeno-associated virus (AAV) was used to deliver the FGF-2 gene to adult RGCs providing a sustained source of this neurotrophic factor. ⋯ Thus the effect of this neurotrophic factor on axon extension could not be solely attributed to an increase in neuronal survival. Our data indicate that selective upregulation of FGF-2 in adult RGCs stimulates axon regrowth within the optic nerve, an environment that is highly inhibitory for regeneration. These results support the hypothesis that key factors involved in axon outgrowth during neural development may promote regeneration of adult injured neurons.
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Mol. Cell. Neurosci. · Sep 2003
Specific involvement in neuropathic pain of AMPA receptors and adapter proteins for the GluR2 subunit.
Chronic pain states arise from peripheral nerve injury and are inadequately treated with current analgesics. Using intrathecal drug administration in a rat model of neuropathic pain, we demonstrate that AMPA receptors play a role in the central sensitisation that is thought to underpin chronic pain. ⋯ We implicate for the first time a possible role for GRIP, PICK1 and NSF in neuropathic sensitisation from experiments with cell-permeable blocking peptides mimicking their GluR2 interaction motifs and also demonstrate differential changes in expression of these proteins following peripheral nerve injury. These studies suggest a critical involvement of protein:protein complexes associated with the AMPA receptor in neuropathic pain, and the possibility that they may have potential as novel therapeutic targets.
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Mol. Cell. Neurosci. · Jun 2003
Lumbar 5 ventral root transection-induced upregulation of nerve growth factor in sensory neurons and their target tissues: a mechanism in neuropathic pain.
We have previously demonstrated that profound and persistent neuropathic pain as displayed by mechanical and cold allodynia and thermal hyperalgesia can be produced by a lumbar 5 ventral root transection (L5 VRT) model in adult rats in which only the motor nerve fibers were injured without axotomy of sensory neurons. However, the underlying mechanisms remain to be determined. In this study, by examining its changes in expression and by inhibiting its functions using a neutralizing antibody, we have investigated whether nerve growth factor (NGF), a neurotrophic factor known to have a function in regulating nerve injury-induced pain, is involved in the development of neuropathic pain induced by L5 VRT. ⋯ NGF protein expression was also increased by sensory neurons with various sizes and by keratinocytes in the target tissue ipsilateral skin. Systemic administration of NGF antiserum twice within 17 days markedly attenuated L5 VRT-induced mechanical allodynia but not the cold allodynia and thermal hyperalgesia. These findings suggest that NGF is an important pain mediator in the generation of mechanical sensitivity induced by L5 VRT.