Neuroscience
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Prolonged nociceptive input following peripheral injury results in hyperalgesia (enhanced response to a noxious stimulus), which is thought to occur as a consequence of sensitization of primary afferent nociceptors and enhanced excitability of spinal dorsal horn nociceptive neurons (central sensitization). Since there is often an expansion of hyperalgesia to tissue adjacent, and even distant from the site of injury (secondary hyperalgesia), it is thought that this phenomenon primarily involves mechanisms of central modulation/plasticity. In contrast, hyperalgesia observed at the site of tissue injury (primary hyperalgesia) involves peripheral mechanisms. ⋯ The effect of bilateral rostral medial medulla lesions produced by the soma-selective neurotoxin ibotenic acid was determined in three different models of cutaneous thermal hyperalgesia following peripheral inflammation: (i) intraplantar injection of carrageenan into the hindpaw (model of primary hyperalgesia); (ii) intra-articular injection of carrageenan/kaolin into the knee of the hind leg (model of secondary hyperalgesia); and (iii) topical application of mustard oil to the hind leg (model of secondary hyperalgesia). Compared with sham lesion animals, a bilateral lesion of the rostral medial medulla completely blocked thermal hyperalgesia in the two models of secondary hyperalgesia (intra-articular carrageenan/kaolin injection into the knee and topical mustard oil application to the hind leg), but was ineffective in blocking facilitation of the thermal paw withdrawal response in the model of primary hyperalgesia (intraplantar carrageenan injection into the hindpaw). These results suggest that primary and secondary hyperalgesia are differentially modulated in the CNS, and support the notion that descending nociceptive facilitatory influences from the rostral medial medulla significantly contribute to secondary, but not primary, hyperalgesia.
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The dorsal regions of the midbrain and pons have been found to participate in sleep regulation. However, the physiological role of the ventral brainstem in sleep regulation remains unclear. We used N-methyl-D-aspartate-induced lesions of the ventral midbrain and pons to address this question. ⋯ These changes are comparable in magnitude to those seen after basal forebrain lesions. Neuronal degeneration was found in the ventral rostral pons and midbrain, including the substantia nigra, ventral tegmental area, retrorubral nucleus, and ventral mesencephalic and rostroventral pontine reticular formation. We conclude that nuclei within the ventral mesencephalon and rostroventral pons play an important role in sleep regulation.
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Noxious mechanical and chemical stimuli were applied to the toes of the left hind limb of decerebrated, spinalized rabbits and their effects on a hind limb spinal withdrawal reflex and expression of Fos-like immunoreactivity in the spinal cord were measured. The animals were prepared so as to minimize nociceptive inputs arising from surgery. A single crush stimulus applied with a pair of haemostatic forceps caused long-lasting (c. 20 min) inhibition of reflexes evoked in medial gastrocnemius motoneurons by electrical stimulation of the skin at the heel. ⋯ Opioid-mediated inhibition of the heel-gastrocnemius withdrawal reflex of the rabbit was evoked by noxious mechanical but not by chemical stimulation of the toes. Of these stimuli, the former gave rise to greater activation of neurons in central and lateral lamina I of segments L7 and S1, the region of termination of afferent fibres from the heel and the location of some enkephalin-positive neuronal cell bodies. Thus, noxious mechanical stimulation of the toes elicits inhibition of the heel-gastrocnemius withdrawal reflex, probably via activation of enkephalinergic neurons in the lateral half of lamina I in the L7 and S1 segments.
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Although it has been shown that unilateral neonatal cortical ablation induces bilateral corticospinal projections, the explanation for the pathways responsible for this bilateral innervation remains controversial. We hypothesized that such reinnervation may be supplied from newly formed fibers sprouting at the level rostral to, or at, or caudal to the pyramidal decussation. In order to test our hypothesis, we examined the brain and spinal cord of young hamsters which had a unilateral ablation of the right motor cortex at six days postnatally, and then received an injection of an anterograde neuronal lectin tracer, Phaseolus vulgaris-leucoagglutinin, into the hindlimb area of the left motor cortex at 21 days postnatally. ⋯ The type I fibers consisted of recrossing axon collaterals sprouted from the intact dorsal funiculus near their targets, while the type II fibers were recrossing parent axons which entered the intact, right gray matter several levels rostral to their targets, and then changed direction toward the targets. The recrossing at lower spinal levels yielded a large number of ipsilaterally labeled axons and their terminals in the gray matter of the denervated lumbar cord, with a distribution pattern similar to that seen on the intact side. The present results indicate that such ipsilateral innervation may play an important role in the sparing and recovery of function following neonatal hemicortical injury.
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The amyloid beta precursor protein can exist as both a membrane-bound and a secreted protein, with the former having the potential to generate the amyloid beta peptide present in the neuritic plaques which are characteristic of Alzheimer's disease. In this study, we have used a clone of the AtT20 mouse pituitary cell line which expresses high levels of the amyloid beta precursor protein to characterize the glycosylation state of the secreted and membrane-bound forms of the protein and to examine the role of post-translational modifications in protein processing. Lectin blot analysis of immunoprecipitated amyloid beta precursor protein demonstrated that the soluble form of the protein contains significant amounts of sialic acid, with the lectin staining being reduced in the particulate cellular fractions. ⋯ The increase in amyloid beta precursor protein levels in the cellular fraction was accompanied by an increase in perinuclear staining. Furthermore, cells overexpressing the alpha2,6(N)-sialyltransferase enzyme also demonstrated an increase in amyloid beta precursor protein secretion. These results suggest that the presence of terminal sialic acid residues on complex-type N-glycans may be required for the optimal transport of the amyloid beta precursor protein from the Golgi to the cell membrane with the subsequent cleavage to generate the secreted form of the protein.