The Journal of neuroscience : the official journal of the Society for Neuroscience
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To elucidate the role of aspartate as a signal molecule in the brain, its localization and those of related amino acids were examined by light and electron microscopic quantitative immunocytochemistry using antibodies specifically recognizing the aldehyde-fixed amino acids. Rat hippocampal slices were incubated at physiological and depolarizing [K+] before glutaraldehyde fixation. At normal [K+], aspartate-like and glutamate-like immunoreactivities were colocalized in nerve terminals forming asymmetrical synapses on spines in stratum radiatum of CA1 and the inner molecular layer of fascia dentata (i.e., excitatory afferents from CA3 and hilus, respectively). ⋯ The synaptic vesicle-to-cytoplasmic matrix ratios of immunogold particle density were similar for aspartate and glutamate, significantly higher than those observed for glutamine or taurine. Similar results were obtained in normoglycemic animals, although the nerve terminal contents of aspartate were lower. The results indicate that aspartate can be concentrated in synaptic vesicles and subject to sustained exocytotic release from the same nerve endings that contain and release glutamate.
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Nociceptor hyper-responsiveness during vincristine-induced painful peripheral neuropathy in the rat.
Neuropathic pain accompanies peripheral nerve injury after a wide variety of insults including metabolic disorders, traumatic nerve injury, and neurotoxic drugs. Chemotherapy-induced neuropathic pain, caused by drugs such as vincristine and taxol, occurs in cancer patients who receive these drugs as antineoplastic agents. Although a variety of remediations have been attempted, the absence of knowledge concerning mechanisms of chemotherapy-induced neuropathic pain has hindered the development of treatment strategies. ⋯ Mean heat and mechanical activation thresholds of C-fiber nociceptors, their distribution among subclasses, and the percentage of spontaneously active neurons in vincristine-treated rats were not statistically different from controls. Vincristine does not, therefore, cause generalized impairment of C-fiber nociceptor function but rather specifically interferes with mechanisms underlying responsiveness to suprathreshold stimuli. Furthermore, vincristine-induced nociceptor hyper-responsiveness may involve alterations specifically in mechanotransduction in some nociceptors and alterations in general cellular adaptation mechanisms in others.
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Comparative Study
Interleukin-1 induces slow-wave sleep at the prostaglandin D2-sensitive sleep-promoting zone in the rat brain.
To determine the site of action of the sleep-promoting effect of interleukin-1 (IL-1), we continuously infused (between 11 P. M. and 5 A. M.) murine recombinant IL-1beta into seven different locations in the ventricular and subarachnoid systems of the brain in freely moving rats. ⋯ The SWS increase caused by IL-1 infusion into the PGD2-SZ was blocked completely by coadministered diclofenac, a nonselective cyclooxygenase (COX) inhibitor. Pretreatment of rats with NS-398 or piroxicam (3 mg/kg of body weight, i.p.), which are said, respectively, to possess high and relative specificity for the COX-2 enzyme, also blocked the SWS-promoting effect of IL-1. We present a hypothesis that IL-1 induces SWS, at least in part, via COX-2-mediated PG production in the PGD2-SZ.