Brain research. Molecular brain research
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Brain Res. Mol. Brain Res. · Sep 2002
Downregulation of voltage-gated potassium channel alpha gene expression in dorsal root ganglia following chronic constriction injury of the rat sciatic nerve.
The hyperexcitability and ectopic spontaneous discharge (ESD) of primary sensory neurons may be important for the generation or maintenance of neuropathic pain. To investigate the relationship between the electrical abnormalities of injured neurons and voltage-gated potassium (Kv) channel gene expression, the expression of the Kv channel alpha genes in the dorsal root ganglion (DRG) was monitored by reverse transcription-polymerase chain reaction (RT-PCR) in a chronic constriction injury (CCI) model of neuropathic pain. Electrophoresis of the RT-PCR products showed the presence of several Kv alpha transcript types with various levels of basal expression in lumbar 4, 5, and 6 DRGs. ⋯ In addition, Kv 1.1 mRNA levels declined to about 72% of the contralateral level at 7 days. No significant changes in Kv 1.5, 1.6, 2.1, 3.1, 3.2, 3.5, and 4.1 mRNA levels were detectable in the ipsilateral DRG at both days. These results suggest that the downregulation of Kv channel alpha gene expression in the DRG following CCI may result in the reduction of K(+) current and contribute to neuronal excitability and ESD generation.
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Brain Res. Mol. Brain Res. · Aug 2002
Involvement of the calcium-independent receptor for alpha-latrotoxin in brain ischemia.
Cerebral ischemia is caused by a reduced blood supply to neurons, and vulnerability to neurodegeneration varies considerably among neuronal types. In hippocampus, neurons in the CA1 region are more susceptible to ischemia-induced neuronal death than neurons in the CA3 region, and in response to transient forebrain ischemia a family of calcium-dependent receptors for alpha-latrotoxin is differentially expressed in the two regions. ⋯ Furthermore, antisense oligonucleotides complementary to CIRL-1 mRNA or CIRL-3 mRNA suppressed neuronal death associated with hypoxia in hippocampal and cortical cell cultures. The observed region-specific CIRL mRNA expression in hippocampus and an in vitro rescue experiment by antisense oligonucleotides against CIRL mRNAs suggest a functional importance of CIRL in neurodegeneration.
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Brain Res. Mol. Brain Res. · Aug 2002
Cell-type-specific expression of protein tyrosine kinase-related receptor RYK in the central nervous system of the rat.
The mammalian RYK is an orphan receptor that contains a catalytically inactive tyrosine-kinase-related domain. Its Drosophila homolog, Lio/Drl, is required for axon pathfinding in developing brain. Our previous study suggested that RYK mRNA is expressed in nestin-positive progenitor cells and neurons. ⋯ In the differentiated stage, expression of RYK was detected in the neurons, but not in type-1 astrocytes. In conclusion, RYK is expressed in nestin-positive progenitor cells and neurons, and in a certain population of oligodendrocytes, O-2A progenitor cells, and type-2 astrocytes in developing CNS. These findings show that expression of RYK in rat CNS is tightly regulated in a cell-type-specific manner.
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Brain Res. Mol. Brain Res. · Jul 2002
Altered expression and phosphorylation of N-methyl-D-aspartate receptors in piglet striatum after hypoxia-ischemia.
The mechanisms for the profound degeneration of striatal neurons after hypoxia-ischemia in newborns are not understood. We hypothesized that this striatal neurodegeneration is related to N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. Using a 1-week-old piglet model of hypoxia-ischemia, we evaluated whether the expression and phosphorylation of NMDA receptor subunits in striatum are modified with severity of evolving neuronal injury after hypoxia-ischemia. ⋯ NR2B levels were increased at 24 h after hypoxia-ischemia. Astrocyte expression of NR2B was prominent after hypoxia-ischemia. We conclude that NMDA receptors are changed in striatum after neonatal hypoxia-ischemia and that abnormal NMDA receptor potentiation through increased NR1 phosphorylation may participate in the mechanisms of striatal neuron degeneration after hypoxia-ischemia.
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Brain Res. Mol. Brain Res. · Mar 2002
Induction of connexin 37 expression in a rat model of neuropathic pain.
Activation of cutaneous C-fibers by capsaicin or sciatic nerve transection increases the number of astrocytic gap junctions as well as the levels of connexin 43 in the dorsal horn on the stimulated side. Changes in connexin 37 mRNA expression following nerve injury have not been previously documented. We examined the role of gap junction protein connexin 37 in neuropathic hypersensitivity following peripheral nerve injury. ⋯ Sciatic nerve connexin 37 mRNA increases were proportional to the extent of thermal hyperalgesia, but skin, muscle, and lumbar spinal cord connexin 37 mRNA showed no significant changes. Neuropathic pain relief correlated with downregulation of connexin 37 mRNA. Results indicate that upregulation of connexin 37 mRNA following sciatic nerve injury correlates with subsequent thermal hyperalgesia, which suggests that gap junctions (connexin 37) are responsible for the hyperexcitability following peripheral nerve injury.