Neuroscience research
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Neuroscience research · Jul 2011
Post-injury administration of minocycline: an effective treatment for nerve-injury induced neuropathic pain.
Neuropathic pain is an intractable clinical problem, affecting millions of people worldwide. Preemptive administration of minocycline has been confirmed useful for treating neuropathic pain by inhibiting spinal microglia activation and consequently lowering proinflammatory cytokine expression. However, most patients with neuropathic pain have no chance to receive preemptive treatment and it remains unclear whether there is a therapeutic time window for post treatment with minocycline. ⋯ Additionally, results from POD 10 and POD 21 showed that intrathecal minocycline suppressed spinal microglia p-p38 expression but without any effects on reversing mechanical allodynia. It is concluded that post-injury intrathecal minocycline is an effective therapeutic intervention for treating SNL-induced neuropathic pain by inhibiting spinal microglia activation. Accordingly, there is indeed a therapeutic time window for post-injury intrathecal minocycline, which is the initiation stage of neuropathic pain development.
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Neuroscience research · Jun 2011
Comparative StudyComparative study of voltage-gated sodium channel α-subunits in non-overlapping four neuronal populations in the rat dorsal root ganglion.
Voltage-gated sodium channel α-subunit (Nav) is the major determinant of neuronal electrophysiological characters. In order to compare the composition of Navs among neurochemically different neurons in the rat dorsal root ganglion (DRG), we examined the expression of Nav transcripts in four non-overlapping neuronal populations, with (+) or without (-) N52 immunoreactivity, a marker of neurons with myelinated axons, and TrkA mRNA identified by in situ hybridization histochemistry. Both N52-/TrkA+ and N52-/TrkA- populations had high levels of signals for Nav1.7, Nav1.8, and Nav1.9 mRNAs, but rarely expressed Nav1.1 or Nav1.6. ⋯ Although, almost no N52+/TrkA- neurons had Nav1.8 or Nav1.9, half of this population expressed Nav1.7 at similar levels to other three populations and the other half completely lacked this channel. These data suggest that Nav1.8 is a common channel for both C- and A-fiber nociceptors, and Nav1.9 is rather selective for C-fiber nociceptors. Nav1.7 is the most universal channel while some functionally unknown N52+/TrkA- subpopulation selectively lacks it.
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Neuroscience research · Jun 2011
Comparative StudyThe ERBB4 intracellular domain (4ICD) regulates NRG1-induced gene expression in hippocampal neurons.
The NRG1 growth factor and ERBB4 receptor have been identified as leading schizophrenia risk genes. Although NRG1 and ERBB4 have been shown to modulate neuronal functions involved in schizophrenia, including both GABAergic and glutamatergic synapses, the exact molecular mechanisms remain poorly understood. Here we investigated ERBB4 intracellular domain, 4ICD, transactivator function in rat hippocampal cultures by inhibiting γ-secretase mediated ERBB4 regulated intramembrane proteolysis (RIP). ⋯ To identify NRG1-4ICD transactivated genes we compared global gene expression profiles of hippocampal cultures stimulated with NRG1 in the absence or presence of CE. In concordance with the contribution of NRG1-ERBB4 signaling to dendritic spine maturation and schizophrenia, global gene expression analysis followed by Ingenuity Pathway Analysis of the dataset identified NRG1-4ICD regulated genes significantly represented in semaphorin signaling and actin cytoskeletal plasticity and multiple genes with confirmed roles in dendritic spine morphogenesis. Using the power of global gene expression analysis our data provides a proof-of-concept supporting a role for non-canonical NRG1-4ICD signaling in the regulation of gene expression contributing to normal and schizophrenic neuronal function.
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Neuroscience research · May 2011
A subset of μ-opioid receptor-expressing cells in the rostral ventromedial medulla contribute to thermal hyperalgesia in experimental neuropathic pain.
The rostral ventromedial medulla (RVM) is a major region for the descending modulation of pain at the spinal cord level, and neurons in the RVM have been implicated in the inhibition and facilitation of spinal nociceptive transmission. Although recent studies have established that the RVM facilitation of nociceptive transmission in the spinal cord contributes to neuropathic pain, the underlying mechanisms remain largely unknown. In the present study, we investigated the effects of kainic acid (KA)-induced RVM damage on neuropathic pain behavior and the expression of molecules implicated in pain modulation. ⋯ KA injection alone did not affect the nocifensive responses to mechanical and thermal stimuli on the intact side. Immunohistochemical analysis revealed that KA injection into the RVM significantly reduced the number of immunoreactive neurons for μ-opioid receptors, but not tryptophan hydroxylase, in association with the analgesic effect. These results suggest that a subset of RVM neurons expressing μ-opioid receptors contribute to the maintenance of thermal hyperalgesia in neuropathic pain.
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Neuroscience research · Mar 2011
Corticospinal tract fibers cross the ephrin-B3-negative part of the midline of the spinal cord after brain injury.
The fibers of corticospinal tract (CST), which control fine motor function, predominantly project to the contralateral spinal cord, not recross to the ipsilateral side. Ephrin-B3, which is expressed in the midline of the spinal cord, and its receptor, EphA4, are crucial for preventing CST fibers from recrossing the midline in the developing spinal cord. However, these fibers can cross the midline to the denervated side after a unilateral CST or cortical injury. ⋯ We found, however, that ephrin-B3 expression in the ventral part of the midline disappeared after postnatal day 9 (P9), but was pronounced along the entire midline before P6. Most of the CST fibers crossed the midline through the ventral region, where ephrin-B3 expression was absent. Our results suggest that ephrin-B3 is not expressed along the entire midline of the spinal cord, and sprouting axons can cross the midline at ephrin-B3-negative areas.