Neuroscience
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We have examined the effect of riluzole, a neuroprotective agent with anticonvulsant properties, on the release of endogenous glutamate from rat cerebrocortical synaptosomes using an on-line enzyme-coupled fluorometric assay. Riluzole inhibited the calcium-dependent release of glutamate that was evoked by exposing cerebrocortical synaptosomes to the potassium channel blocker 4-aminopyridine, and this presynaptic inhibition was concentration-dependent. Riluzole did not alter either 4-aminopyridine-evoked depolarization of the synaptosomal membrane potential or ionomycin-mediated glutamate release, indicating that riluzole-mediated inhibition of glutamate release is not due to a decrease in synaptosomal excitability or a direct effect on the exocytotic machinery. ⋯ It is concluded that riluzole exerts their presynaptic inhibition, likely through a reduction in the calcium influx mediated by P/Q-type calcium channels, and thereby inhibits the release of glutamate from rat cerebrocortical nerve terminals. This release inhibition may involve a pertussis toxin-sensitive G protein signalling pathway. This finding provides further support that presynaptic calcium channel blockade concomitant with inhibition of glutamate release could be an important mechanism underlying the therapeutic actions of this drug.
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For many years, research focus on metallothioneins, small zinc binding proteins found predominantly within astrocytes in the brain, has centred on their ability to indirectly protect neurons from oxygen free radicals and heavy metal-induced neurotoxicity. However, in recent years it has been demonstrated that these proteins have previously unsuspected roles within the cellular response to brain injury. The aim of this commentary is to provide an overview of the exciting recent experimental evidence from several laboratories including our own suggesting a possible extracellular role for these proteins, and to present a hypothetical model explaining the newly identified function of extracellular metallothioneins in CNS injury and repair.
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The enteric nervous system plays an integral role in the gastrointestinal tract. Within this intricate network, enteric glia are crucial in the maintenance of normal bowel function, yet their signaling mechanisms are poorly understood. Enteric glia, and not enteric neurons, selectively responded to lysophosphatidic acid (LPA), a product of phosphatidylcholine metabolism, with dose-dependent calcium (Ca(2+)) signaling over a range from 100 pM to 10 microM. ⋯ Inhibition of the inositol 1,4,5-trisphosphate (IP(3)) receptor with 200 microM 2-aminoethoxydiphenylborate (2APB) abolished LPA signals. RT-PCR analysis demonstrated the presence of two LPA-coupled endothelial differentiation gene (EDG) receptor mRNAs (EDG-2 and EDG-7) in myenteric plexus primary cultures. EDG-2 expression in glial cells of the ENS was confirmed immunocytochemically.
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Audiogenic seizures are a model of generalized tonic-clonic brainstem-generated seizures. Repeated induction of audiogenic seizures, in audiogenic kindling (AuK) protocols, generates limbic epileptogenic activity. The present work evaluated associations between permanence of AuK-induced limbic epileptogenicity and changes in cell number/gluzinergic terminal reorganization in limbic structures in Wistar audiogenic rats (WARs). ⋯ AmK and AuK-AmK were associated with broader cell loss than AuK. Data indicate that permanent AuK-induced limbic epileptogenicity is mainly associated to gluzinergic terminal reorganization in amygdala but not in the hippocampus and with no hippocampal cell loss. Few AmK-induced seizures are associated to broader and higher cell loss than a higher number of AuK-induced seizures.
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Comparative Study
Synaptic properties and postsynaptic opioid effects in rat central amygdala neurons.
An important output of amygdaloid nuclei, the central nucleus of the amygdala (CeA) not only mediates negative emotional behaviors, but also participates in the stimulus-reward learning and expression of motivational aspects of many drugs of abuse, and links environmentally stressful conditions such as fear to endogenous pain-inhibiting mechanisms. The endogenous opioid system in the CeA is crucial for both reward behaviors and environmental stress-induced analgesia. In this study using whole-cell voltage-clamp recordings, we investigated synaptic inputs and the postsynaptic effects of opioid agonists in CeA neurons. ⋯ In contrast, the kappa-opioid receptor agonist hyperpolarized only type B neurons. These results illustrate three types of CeA neurons with distinctive membrane properties and differential responses to opioid agonists. They may represent functionally distinct CeA cell groups for the integration and execution of CeA outputs in the aforementioned CeA functions.