Neuroscience
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Administration of cocaine to pregnant rabbits produces robust and long-lasting anatomical alterations in the dopamine-rich anterior cingulate cortex of offspring. These effects include increased length and decreased bundling of layer III and V pyramidal neuron dendrites, increases in parvalbumin expression in the dendrites of interneurons, and increases in detectable GABAergic neurons. We have now examined multiple cortical regions with varying degrees of catecholaminergic innervation to investigate regional variations in the ability of prenatal cocaine exposure to elicit these permanent changes. ⋯ These regions included the medial prefrontal, entorhinal, and piriform cortices. In contrast, primary somatosensory, auditory and motor cortices exhibited little tyrosine hydroxylase staining and no measurable cocaine-induced changes in cortical structure. From these data we suggest that the presence of dopaminergic afferents contributes to the marked specificity of the altered development of excitatory pyramidal neurons and inhibitory interneurons induced by low dose i.v. administration of cocaine in utero.
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Research using animal models of neuropathic pain has revealed sympathetic sprouting onto dorsal root ganglion cells. More recently, sensory fibre sprouting onto dorsal root ganglion cells has also been observed. Previous work in our laboratory demonstrated persistent sympathetic fibre sprouting in the skin of the rat lower lip following sensory denervation of this region. ⋯ These results indicate that sympathectomies lead to transient changes in substance P-immunoreactive fibre innervation and neurokinin-1 receptor expression in rat lower lip skin. The effects are most prominent in the lower dermis probably due to a greater local concentration of nerve growth factor in this region. The plasticity of the interactions between sensory and sympathetic fibres may prove important in the regulation of skin microcirculation and in the generation of painful sensations under normal conditions or following peripheral nerve injuries.
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Dextran-conjugated Ca(2+) indicators were injected into the accessory olfactory bulb of frogs in vivo to selectively fill presynaptic terminals of mitral cells at their termination in the ipsilateral amygdala. After one to three days of uptake and transport, the forebrain hemisphere anterior to the tectum was removed and maintained in vitro for simultaneous electrophysiological and optical measurements. Ca(2+) influx into these terminals was compared to synaptic transmission between mitral cells and amygdala neurons under conditions of reduced Ca(2+) influx resulting from reduced extracellular [Ca(2+)], blockade of N- and P/Q-type channels, and application of the cholinergic agonist carbachol. ⋯ Carbachol (100 microM) acting via muscarinic receptors had no effect on the afferent volley, but rapidly and reversibly reduced Ca(2+) influx through both N- and P/Q-type channels by 51% and postsynaptic responses by 78%, i.e. release was proportional to Ca(2+) raised to the power approximately 2.5. The weak dependence of release on changes in Ca(2+) when channel toxins block channels suggests little overlap between Ca(2+) microdomains from channels supporting release or substantial segregation of channel subtypes between terminals. The proportionately greater reduction of transmission by muscarinic receptors compared to Ca(2+) channel toxins suggests that they directly affect the release machinery in addition to reducing Ca(2+) influx.
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Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. ⋯ Metallothioneins-I+II proteins were prominent in areas of induced cellular infiltrates. Reactive astrocytes and activated monocytes/macrophages were the sources of metallothioneins-I+II proteins. From these results we suggest that metallothioneins-I+II but not metallothionein-III may play an important role during experimental autoimmune encephalomyelitis, and indicate that the pro-inflammatory cytokine interferon-gamma is unlikely an important factor in this response.
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Gap junctions, which serve as intercellular channels providing direct cytoplasmic continuity and ionic current flow between adjacent cells, are constituted by connexin proteins. Using an in vitro model of bicuculline-induced epileptiform activity, we asked whether increased connexin levels occur during epileptiform activity in the intact whole hippocampus, freshly isolated from young (15-day-old) mouse brain. Exposure to bicuculline (10 microM), for 2-10 h, induced persistent changes in electrical activities that included enhanced spontaneous field activity (4 h), an epileptiform response to single electrical stimulation (6 h), and spontaneous epileptiform activity (6 h). ⋯ After 2-6 h exposure to bicuculline, the connexin 32 mRNA expression was upregulated to 2-3-fold control (P < 0.01), and its protein level was significantly elevated the following 6 h (P < 0.01), at which time electrophysiologically measured evidence of clearly epileptiform activity was apparent. In addition, the transcription factor, c-fos protein, but not the cAMP response element-binding protein, was also found to be increased at the early stage of bicuculline exposure (2 h) compared to control (P < 0.05). Thus, we have found that exposing the acutely isolated hippocampus to bicuculline, induced increased c-fos protein, followed by increased connexin 32 transcript and protein, and concurrently, persistent epileptiform activity that was depressed by carbenoxolone.