Neuroscience
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In various chemoconvulsant models of human temporal lobe epilepsy, the induction of epileptogenesis by a prolonged period of continuous seizure activity is accompanied by significant changes in hippocampal structure. These changes include an increase in neurogenesis within the proliferative subgranular zone (SGZ) of the dentate gyrus and induction of mossy fiber sprouting in mature dentate granule cells. As dentate granule cell neurogenesis and axon outgrowth are also hallmarks of hippocampal development, we hypothesized that molecules involved in normal development may also play a role in similar changes associated with epileptogenesis. ⋯ Patterns of expression varied considerably between family members, ranging from the limited expression of Mash1 in the neurogenic SGZ of the dentate gyrus to the scattered, widespread profile of Hes5 throughout the dentate gyrus and the hippocampus proper. Moreover, these varied profiles of expression were differentially regulated following status epilepticus, with some increasing (Mash1, Id2), some falling (Hes5, Prox1), and others remaining mostly unchanged (NeuroD/BETA2, NeuroD2/NDRF, Id3, Rath2/Nex1). While the function of these molecules in the adult brain remains to be characterized, our findings support the idea that molecules controlling cell-fate decisions in the developing dentate gyrus are also operative during seizure-induced neurogenesis and plasticity.
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We examined the effects of the neuropeptide nociceptin/orphanin FQ on activity of the limbic-hypothalamic-pituitary-adrenal axis (also known as the stress axis) in rats. This axis regulates important metabolic functions, and initiates critical neuroendocrine responses that cope with environmental threats and challenges to homeostatic functioning. Disregulation of the limbic-hypothalamic-pituitary-adrenal axis is associated with impaired physical and psychological health. ⋯ We conclude that administration of nociceptin/orphanin FQ activates neuroendocrine activity of the limbic-hypothalamic-pituitary-adrenal axis even in the absence of a stressor, and may delay the shutdown of these physiological responses after exposure to acute mild stress. In light of the known functions of this axis, it appears that nociceptin/orphanin FQ participates in the regulation of important metabolic functions, and may be implicated in physiological responses to stress. This interaction between nociceptin/orphanin FQ and the limbic-hypothalamic-pituitary-adrenal axis implicates nociceptin/orphanin FQ in important aspects of physiological and psychological well-being.
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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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The contact with the postsynaptic target induces structural and functional modifications in the serotonergic cell C1 of Helix pomatia. In previous studies we have found that the presence of a non-physiological target down-regulates the number of presynaptic varicosities formed by cultured C1 neurons and has a strong inhibitory effect on the action potential-evoked Ca(2+) influx and neurotransmitter release at C1 terminals. Since a large body of experimental evidence implicates the synapsins in the development and functional maturation of synaptic connections, we have investigated whether the injection of exogenous synapsin I into the presynaptic neuron C1 could affect the inhibitory effect of the wrong target on neurotransmitter release. ⋯ A three-fold increase in the amplitude of the sniffer depolarization with respect to the pre-injection amplitude (190+/-29% increase, n=10, P<0.006) was found 5 min after injection of Ca(2+)/calmodulin-dependent protein kinase II-phosphorylated synapsin I that lasted for about 30 min. No significant change was observed after injection of buffer or dephosphorylated synapsin I. These data indicate that the presence of synapsin I induces a fast increase in neurotransmitter release that overcomes the inhibitory effect of the non-physiological target and suggest that the expression of synapsins may play a role in the modulation of synaptic strength and neural connectivity.
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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.