Brain research. Molecular brain research
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Brain Res. Mol. Brain Res. · Nov 2001
Changes in voltage-gated calcium channel alpha(1) gene expression in rat dorsal root ganglia following peripheral nerve injury.
Although an increase in the excitability and ectopic spontaneous discharge (ESD) of primary sensory neurons can lead to abnormal burst activity, which is associated with neuropathic pain, the underlying molecular mechanisms are not fully understood. To investigate the relationship between these electrical abnormalities in injured neurons and voltage-gated calcium channel (VGCC) gene expression, reverse transcription-polymerase chain reaction (RT-PCR) was used to monitor the expression of the VGCC alpha(1) gene in the dorsal root ganglion (DRG) following chronic constriction injury (CCI) and axotomy of the rat sciatic nerve. ⋯ The same transcripts were repressed 7 days after sciatic axotomy and their reduction levels proved similar to those of CCI. Considering that changes of the intracellular calcium concentration modify the maintenance of ESD in injured DRG, these results suggest that the downregulation of alpha(1C), alpha(1D), alpha(1H) and alpha(1I) subunit gene expression in the rat DRG following peripheral nerve injury may contribute to the production of ESD associated with damaged nerves.
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Brain Res. Mol. Brain Res. · Nov 2001
Changes in AMPA receptor binding and subunit messenger RNA expression in hippocampus and cortex in the pentylenetetrazole-induced 'kindling' model of epilepsy.
'Kindling' is a phenomenon of epileptogenesis, which has been widely used as an experimental model of temporal lobe epilepsy. In the present study, we have examined the contribution of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptors and their subunits (GluR-A, -B, -C and -D) to the acquisition and maintenance of the kindled state in the pentylenetetrazole (PTZ)-induced 'kindling' mouse model, by using quantitative autoradiography and in situ hybridization. Region-specific increases in [3H]AMPA binding were seen in kindled animals in the CA3 region of hippocampus and in the temporal cortex 1 week after the last PTZ injection. ⋯ At 1 month after the last PTZ injection, an upregulation in [3H]AMPA binding appeared in the motor cortex and the basal ganglia of kindled animals, which is consistent with electrophysiological data showing hyperexcitability in the cortex of the PTZ-kindled animals at that time. Interestingly, an increase in mRNA for the GluR-B subunit appeared in the outer layers of motor and somatosensory cortices of the kindled animals 1 month after acquisition of the kindled state, possibly as part of a gene-regulated, compensatory mechanism against seizure susceptibility, since this change should give rise to a higher proportion of Ca(2+)-impermeable AMPA receptors. These results support the evidence of a transient role of hippocampal AMPA receptors in the acquisition of the 'kindling' phenomenon and they also suggest an involvement of AMPA receptors in the maintenance of kindled state at least in two brain areas, cortex and basal ganglia.
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Brain Res. Mol. Brain Res. · Nov 2001
Difference in binding by isolectin B4 to trkA and c-ret mRNA-expressing neurons in rat sensory ganglia.
The neurons labeled by isolectin B4 (IB4) in rat and mouse sensory ganglia are often regarded as non-nerve growth factor (NGF)-dependent and non-peptidergic neurons, but a considerable number of IB4-positive neurons in the dorsal root ganglion (DRG) are also shown to be immunoreactive to substance P (SP) and calcitonin gene-related peptide (CGRP), which are synthesized by NGF-dependent neurons. Therefore, we examined the relationships between the IB4-binding neurons and NGF/glial cell line-derived neurotrophic factor (GDNF)/GDNF-related proteins(GDNFs)-dependent neurons in rat DRGs by use of in situ hybridization histochemistry in serial sections. Of the DRG neurons, 42% and 22% were intensely and weakly labeled by IB4, respectively. ⋯ On the other hand, 66% and 10% of the c-ret mRNA-expressing neurons were intensely and weakly labeled, respectively. The mRNA of somatostatin, another major neuropeptide in the sensory neurons, was exclusively expressed in the intensely IB4-labeled neurons. These findings suggest that many NGF-dependent and peptidergic sensory neurons are labeled by IB4 in rats.
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Brain Res. Mol. Brain Res. · Nov 2001
The changes in expression of three subtypes of TTX sensitive sodium channels in sensory neurons after spinal nerve ligation.
Our previous studies showed that the ectopic discharges in injured sensory neurons and mechanical allodynia that developed after spinal nerve ligation were significantly reduced by application of a low concentration of tetrodotoxin (TTX) to the corresponding dorsal root ganglion (DRG) of the ligated spinal nerve. Based on these data, we hypothesized that expression of TTX-sensitive sodium channels is up-regulated in the injured sensory neurons and that such up-regulation plays an important role in the generation of ectopic discharges and thus pain behaviors in spinal nerve ligated neuropathic rats. To test this hypothesis, the present study examined the changes in three subtypes of TTX-sensitive sodium channels in the DRG after spinal nerve ligation. ⋯ Type III immunoreactivity was found preferentially in medium to large sized neurons. Thus the majority of neurons with cell bodies having diameters > or =40 microm became type III-positive after nerve ligation. The data indicate that the increased expression of type III sodium channels in axotomized sensory neurons may be the critical factor for the TTX sensitivity of ectopic discharges in injured sensory neurons and thus the generation of ectopic discharges and neuropathic pain behaviors in spinal nerve ligated rats.
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Brain Res. Mol. Brain Res. · Nov 2001
Dorsal root ganglion neurons show increased expression of the calcium channel alpha2delta-1 subunit following partial sciatic nerve injury.
Neuropathic pain is associated with changes in the electrophysiological and neurochemical properties of injured primary afferent neurons. A mRNA differential display study in rat L(4/5) dorsal root ganglia (DRGs) revealed upregulation of the calcium channel alpha2delta-1 subunit 2 weeks after partial sciatic nerve ligation (Seltzer model of neuropathic pain). The upregulated transcript appeared to represent previously unidentified sequence from the 3'-untranslated region of rat alpha2delta-1 mRNA. ⋯ The most intensely labelled neuronal profiles in ipsilateral, sham and contralateral DRGs, were generally those with small cross-sectional areas. The alpha2delta-1 auxiliary subunit is known to modulate calcium channel function in heterologous expression systems via its association with the pore-forming alpha1 calcium channel subunit. Therefore the increased levels of this subunit in the populations of primary afferents described may, via modulation of calcium-dependent processes such as neurotransmitter release and neuronal excitability, influence the processing of sensory information.