Journal of neurochemistry
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Journal of neurochemistry · Jan 2008
Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons.
It has previously been observed that expression of chemokine monocyte chemoattractant protein-1 (MCP-1/CC chemokine ligand 2 (CCL2)) and its receptor CC chemokine receptor 2 (CCR2) is up-regulated by dorsal root ganglion (DRG) neurons in association with rodent models of neuropathic pain. MCP-1 increases the excitability of nociceptive neurons after a peripheral nerve injury, while disruption of MCP-1/CCR2 signaling blocks the development of neuropathic pain, suggesting MCP-1 signaling is responsible for heightened pain sensitivity. To define the mechanisms of MCP-1 signaling in DRG, we studied intracellular processing, release, and receptor-mediated signaling of MCP-1 in DRG neurons. ⋯ MCP-1 expressed by DRG neurons was packaged into large dense-core vesicles whose release could be induced from the soma by depolarization in a Ca2+-dependent manner. Activation of CCR2 by MCP-1 could sensitize nociceptors via transactivation of transient receptor potential channels. Our results suggest that MCP-1 and CCR2, up-regulated by sensory neurons following peripheral nerve injury, might participate in neural signal processing which contributes to sustained excitability of primary afferent neurons.
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Journal of neurochemistry · Jan 2008
Effect of glutamate intake during gestation on adenosine A(1) receptor/adenylyl cyclase pathway in both maternal and fetal rat brain.
Pregnant Wistar rats were orally treated with 1 g/L l-glutamate during the entire gestational period and the status of adenosine A(1) receptor (A(1)R)/adenylyl cyclase transduction pathway from maternal and fetal brain was analyzed. Glutamate consumption, estimated from the loss of water from the drinking bottles, was 110 +/- 4.6 mg/kg/day. In mother brains glutamate intake did not significantly alter the B(max) value, although the K(d) value was significantly decreased. ⋯ On the other hand, basal, forskolin, and forskolin plus GTPgammaS-stimulated adenylyl cyclase activity was significantly decreased in both maternal and fetal brain, and this was more prominent in fetal than in maternal brain. Finally, A(1)R functionality was significantly decreased in mother brain whereas no significant differences were detected in fetus brain. These results suggest that glutamate administered to pregnant rats modulates A(1)R signaling pathways in both tissues, showing an A(1)R down-regulation in fetal brain, and desensitization in maternal brain.
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Journal of neurochemistry · Jan 2008
Chondroitinase ABC has a long-lasting effect on chondroitin sulphate glycosaminoglycan content in the injured rat brain.
Chondroitin sulphate proteoglycans (CSPGs) are axon growth inhibitory molecules present in the glial scar that play a part in regeneration failure after damage to the CNS and which restrict CNS plasticity. Removal of chondroitin sulphate glycosaminoglycan (GAG) chains with chondroitinase-ABC (chABC) in models of CNS injury promotes both axon regeneration and plasticity. We have analysed the immediate and long-term effects of a single injection of chABC on CSPGs, GAGs and axon regeneration. ⋯ This suggests the persistence of active chABC for at least 10 days after injection which is able to digest CSPGs released from cells during this time. This was confirmed by immunological detection of enzyme for 10 days and by retrieval of active enzyme from the brain at 10 days after injection. Our results suggest that a single injection of chABC can produce an environment conducive to CNS repair for over 10 days.
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Journal of neurochemistry · Jan 2008
Glial cell-derived glutamate mediates autocrine cell volume regulation in the retina: activation by VEGF.
Astroglial cells are a source for gliotransmitters such as glutamate and ATP. We demonstrate here that gliotransmitters have autocrine functions in the regulation of cellular volume. Hypoosmotic stress in the presence of inflammatory mediators or oxidative stress, and during blockade or down-regulation of potassium channels, induces swelling of retinal glial cells. ⋯ This cascade involved the release of ATP and adenosine, and the activation of purinergic P2Y(1) and adenosine A1 receptors, resulting in the opening of potassium and chloride channels and inhibition of cellular swelling. The glutamatergic-purinergic regulation of the glial cell volume may be functionally important in the homeostasis of the extracellular space volume during intense neuronal activation which is associated with a swelling of neuronal cell structures in the retina. However, glial cell-derived glutamate may also contribute to the swelling of activated neurons since metabolic poisoning of glial cells by iodoacetate inhibits the neuronal cell swelling mediated by activation of ionotropic glutamate receptors.