Neuroscience research
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Neuroscience research · Nov 1999
Lipopolysaccharide-induced microglial activation in culture: temporal profiles of morphological change and release of cytokines and nitric oxide.
Microglial activation has been considered as a result of neuronal damage, however, recently it becomes to recognize as a possible cause of the damage in various neurodegenerative diseases. To elucidate the mechanism of the microglial activation, we examined the time course of lipopolysaccharide (LPS)-induced change in morphology and the release of cytokines and nitric oxide (NO) in cultured microglia from neonatal rat brains. With addition of 1 microg/ml LPS, the cell morphology was drastically changed within 3 h from amoeboid shape to bipolar rod shape. ⋯ The addition of dibutyryl cAMP markedly inhibited the release of TNF-alpha and IL-1beta, but not IL-6 and NO at all. These results suggest that there are at least two different intracellular signaling pathways of LPS-induced microglial activation; one for early release of TNF-alpha and IL-1beta sensitive to dibutyryl-cAMP and the other for late release of IL-6 and NO insensitive to dibutyryl-cAMP. The transient morphological change seems to be associated with the early release based on the sensitivity to dibutyryl-cAMP.
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Neuroscience research · Nov 1999
Itch-associated response induced by intradermal serotonin through 5-HT2 receptors in mice.
Serotonin (5-HT) is pruritogenic in humans and suggested to be involved in some pruritic diseases. Our experiments were carried out to determine whether an intradermal injection of 5-HT would elicit itch-associated response in mice and to elucidate the 5-HT receptor subtypes involved in this 5-HT action. 5-HT (14.1-235 nmol site(-1)) injected intradermally into the rostral back elicited scratching of the injected site, with bell-shaped dose-response relationship. The scratching induced by 5-HT (100 nmol site(-1), peak effective dose) was suppressed by capsaicin (repeated administration) and the opioid antagonist naloxone, features being similar to human itching. ⋯ Peroral pretreatment with 5-HT3 receptor antagonists ondansetron and 3-tropanyl-3, 5-dichrobenzoate did not significantly suppress 5-HT-induced scratching. The results suggest that scratching induced by intradermal injection of 5-HT is itch-associated response. The 5-HT action may be mediated at least partly by cutaneous 5-HT2 receptors.