Journal of neurobiology
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General anesthetics abolish behavioral responsiveness in all animals, and in humans this is accompanied by loss of consciousness. Whether similar target mechanisms and behavioral endpoints exist across species remains controversial, although model organisms have been successfully used to study mechanisms of anesthesia. In Drosophila, a number of key mutants have been characterized as hypersensitive or resistant to general anesthetics by behavioral assays. ⋯ Finally, genetic and pharmacological analysis revealed that anesthetic sensitivities in the fly brain are, like other arousal states, influenced by dopaminergic activity. These results suggest that volatile anesthetics such as isoflurane may target the same processes that sustain wakefulness and attention in the brain. LFP correlates of general anesthesia in Drosophila provide a powerful new approach to uncovering the nature of these processes.
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Journal of neurobiology · Aug 2006
Faster nerve regeneration after sciatic nerve injury in mice over-expressing basic fibroblast growth factor.
Basic fibroblast growth factor (FGF-2) is expressed in the peripheral nervous system and is up-regulated after nerve lesion. It has been demonstrated that administration of FGF-2 protects neurons from injury-induced cell death and promotes axonal regrowth. Using transgenic mice over-expressing FGF-2 (TgFGF-2), we addressed the importance of endogenously generated FGF-2 on sensory neuron loss and sciatic nerve regeneration. ⋯ To study the role of FGF-2 over-expression on Schwann cell proliferation during the early regeneration process, we used BrdU-labeling to mark dividing cells. In transgenic mice, the number of proliferating cells was significantly increased distal to the crush site compared to wild-types. We propose that endogenously synthesized FGF-2 influences early peripheral nerve regeneration by regulating Schwann cell proliferation, axonal regrowth, and remyelination.
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Journal of neurobiology · Mar 2006
Transcriptional profiling of brain-derived-neurotrophic factor-induced neuronal plasticity: a novel role for nociceptin in hippocampal neurite outgrowth.
Brain derived neurotrophic factor (BDNF) exhibits a sequence of actions on neurons ranging from acute enhancement of transmission to long-term promotion of neurite outgrowth and synaptogenesis associated with learning and memory. The manifold effects of BDNF on neuronal modifications may be mediated by genomic alterations. We previously found that BDNF treatment acutely increases transcription of the synaptic vesicle protein Rab3A, required for trophin-induced synaptic plasticity, as well as the peptide VGF, which increases during learning. ⋯ To examine the significance of activation, the effects of nociceptin (orphanin FQ) and nocistatin on neurite outgrowth were examined. Quantitative morphometric analysis revealed that nociceptin significantly increased both average neurite length and average number of neurites per neuron, while nocistatin had no effect on these parameters. These results reveal a novel role for nociceptin and suggest that these neuropeptide systems may contribute to the regulation of neuronal function by BDNF.
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Acute, inflammatory, and neuropathic pain can all be attenuated or abolished by local treatment with sodium channel blockers such as lidocaine. The peripheral input that drives pain perception thus depends on the presence of functional voltage-gated sodium channels. ⋯ A combination of antisense and knock-out studies support a specialized role for these sodium channels in pain pathways, and pharmacological studies with conotoxins suggest that isotype-specific antagonists should be feasible. Taken together, these data suggest that isotype-specific sodium channel blockers could be useful analgesics.
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Although the opioids are the principal treatment options for moderate to severe pain, their use is also associated with the development of tolerance, defined as the progressive need for higher doses to achieve a constant analgesic effect. The mechanisms which underlie this phenomenon remain unclear. ⋯ CCK is both antiopioid and pronociceptive, and activates descending pain facilitation mechanisms from the RVM enhancing nociceptive transmission at the spinal cord and promoting hyperalgesia. The neuroplastic changes elicited by opioid exposure reflect adaptive changes to promote increased pain transmission and consequent diminished antinociception (i.e., tolerance).