Neuroscience
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Comparative Study
Different roles of nitric oxide synthase-1 and -2 between herpetic and postherpetic allodynia in mice.
We investigated using the mice role of nitric oxide synthase (NOS) in the spinal dorsal horn in herpetic and postherpetic pain, especially allodynia, which was induced by transdermal inoculation of the hind paw with herpes simplex virus type-1 (HSV-1). The virus inoculation induced NOS2 expression in the lumbar dorsal horn of mice with herpetic allodynia, but not postherpetic allodynia. There were no substantial alternations in the expression level of NOS1 at the herpetic and postherpetic stages. ⋯ The expression level of NOS1 mRNA in the dorsal root ganglia was similar between mice with and without postherpetic allodynia. The results suggest that herpetic and postherpetic allodynia is mediated by nitric oxide in the dorsal horn and that NOS2 and NOS1 are responsible for herpetic and postherpetic allodynia, respectively. It may be worth testing the effects of NOS2 and NOS1 inhibitors on herpetic pain and postherpetic neuralgia in human subjects, respectively.
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Modulation of membrane properties and excitability of retinal ganglion cells (RGCs) by dopamine was investigated in rat retinal slices, using whole cell patch clamp techniques. Application of dopamine (10 microM) caused a small depolarization of the membrane potential, a reduction of the input resistance and a decrease in the number of current-evoked action potentials of RGCs, and these effects were blocked by a D1 antagonist (SCH23390, 10 microM), but not by a D2 antagonist (sulpiride, 10 microM). SKF38393 (10 microM), a D1 agonist, but not quinpirole (10 microM), a D2 agonist, mimicked the effects of dopamine on RGCs. ⋯ SKF38393 and 8-Br-cAMP increased the amplitude of I(h), which was blocked by KT5720. The dopamine effects were abolished when the preparations were pre-incubated by ZD7288. These data strongly suggest that the dopamine effects on rat RGCs may be, at least in part, mediated by modulation of I(h) through the cAMP- and PKA-dependent pathway.
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The fenestrated microvasculature of the area postrema shows a less restrictive blood-brain barrier than is found in other areas of the CNS. We have studied the expression and relationship of vascular endothelial tight junctional proteins, astrocytes, macrophages, and the extracellular matrix with the extravasation of fluorescently tagged dextrans and sodium fluorescein in the rat area postrema. Glial fibrillary acidic protein (GFAP) -positive astrocytes were present within the area postrema which was surrounded by a dense zone of highly GFAP-reactive astrocytes. ⋯ Three-kilodalton dextran diffused into the parenchyma, but was retained within the boundary of the area postrema at the interface with the highly reactive GFAP-astrocytes, while sodium fluorescein (0.3 kDa) passed from the area postrema into surrounding CNS areas. Our observations suggest that despite the absence of a tight blood-brain barrier, a size selective barrier restricting the movement of blood solutes into the parenchyma is present in the area postrema. We suggest that the rapid uptake by CD163 and CD169 macrophages together with the non-fused laminin immunoreactive layers of the extracellular matrix plays a size selective role in restricting movement of serum proteins and other blood borne macromolecules over 10 kDa in to the area postrema.
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Tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme in 5-HT synthesis in the brain, is a candidate for participation in a mechanism mediating the antidepressant effect of selective 5-HT reuptake inhibitors such as fluoxetine. Using real-time reverse transcription-polymerase chain reaction (RT-PCR) and semi-quantitative RT-PCR techniques, we have examined the effects of fluoxetine administration with drinking water (7.5 mg/kg/day) for 2, 4 and 8 weeks on TPH2 mRNA expression in the midbrain part of the dorsal raphe nucleus (DRN) and in the brainstem containing the rest of the raphe complex. Fluoxetine treatment for 4 and 8 weeks significantly increased basal TPH2 mRNA levels in the midbrain, an effect that was correlated with the appearance of antidepressant-like effects in the forced swim test. ⋯ In these animals, the swim test also produced a marked decrease in 5-HT metabolite (5-hydroxyindoleacetic acid (5-HIAA)) content in the amygdala. Fluoxetine treatment for 4 and 8, but not for 2 weeks, abolished these swim-induced changes in TPH2 and 5-HTT mRNAs levels in the midbrain and 5-HIAA content in the amygdala. The results of the present study suggest that TPH2 gene expression in the midbrain part of the DRN is implicated in depression and stress response, as well as in the antidepressant fluoxetine action.
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The intergeniculate leaflet (IGL) is a flat thalamic nucleus that responds to retinal illumination, but also to non-photic input from many brain areas. Its only known function is to modulate the circadian rhythm generated by the suprachiasmatic nucleus. Previously, the firing behavior of cells in IGL has been investigated with extra-cellular recordings, but intracellular recordings from morphologically identified mammalian IGL neurons are lacking. ⋯ This suggests that spontaneous activity was controlled by several, yet undetermined factors in addition to membrane potential. Within the IGL we found a broad range of morphologies without apparent categories and no significant correlation with activity. However, the spontaneous, usually regular, spiking and the rebound depolarization of IGL cells is typical a feature that distinguish them from neurons in ventral and from interneurons in the dorsal lateral geniculate nuclei.