Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypocretin has been identified as a regulator of metabolic and endocrine systems. Several brain regions involved in the central regulation of autonomic and endocrine processes or attention are targets of extensive hypocretin projections. The most dense arborization of hypocretin axons in the brainstem was detected in the locus coeruleus (LC). Multiple labeling immunocytochemistry revealed a massive synaptic innervation of catecholaminergic LC cells by hypocretin axon terminals in rats and monkeys. In both species, all tyrosine hydroxylase-immunopositive cells in the LC examined by electron microscopy were found to receive asymmetrical (excitatory) synaptic contacts from multiple axons containing hypocretin. In parallel electrophysiological studies with slices of rat brain, all LC cells showed excitatory responses to the hypocretin-2 peptide. Hypocretin-2 uniformly increased the frequency of action potentials in these cells, even in the presence of tetrodotoxin, indicating that receptors responding to hypocretin were expressed in LC neurons. Two mechanisms for the increased firing rate appeared to be a reduction in the slow component of the afterhyperpolarization (AHP) and a modest depolarization. Catecholamine systems in other parts of the brain, including those found in the medulla, zona incerta, substantia nigra or olfactory bulb, received significantly less hypocretin input. Comparative analysis of lateral hypothalamic input to the LC revealed that hypocretin-containing axon terminals were substantially more abundant than those containing melanin-concentrating hormone. The present results provide evidence for direct action of hypothalamic hypocretin cells on the LC noradrenergic system in rats and monkeys. Our observations suggest a signaling pathway via which signals acting on the lateral hypothalamus may influence the activity of the LC and thereby a variety of CNSfunctions related to noradrenergic innervation, including vigilance, attention, learning, and memory. Thus, the hypocretin innervation of the LC may serve to focus cognitive processes to compliment hypocretin-mediated activation of autonomic centers already described.
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PMID:Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system. 1054 56

Orexin-A-like immunoreactive (OrA-ir) neurons and terminals in the cat hypothalamus were examined using immunohistochemical techniques. OrA-ir neurons were found principally in the lateral hypothalamic area (LHA) at the level of the tuberal cinereum and in the dorsal and posterior hypothalamic areas. In the LHA the majority of the neurons were located dorsal and lateral to the fornix; a small number of OrA-ir neurons were also present in other regions of the hypothalamus. OrA-ir fibers with varicose terminals were detected in almost all hypothalamic regions. The high density of fibers was located in the suprachiasmatic nucleus, the infundibular nucleus (INF), the tuberomamillary nucleus (TM) and the supra- and pre-mamillary nuclei. Ultrastructural analysis revealed that OrA-ir neurons in the LHA receive abundant input from non-immunoreactive terminals. These terminals, which contained many small, clear, round vesicles with a few large, dense core vesicles, made asymmetrical synaptic contacts with OrA-ir dendrites, indicating that the activity of orexin neurons is under excitatory control. On the other hand, the terminals of OrA-ir neurons also made asymmetrical synaptic contact with dendrites in the LHA, the INF and the TM. The dendrites in the LHA were both non-immunoreactive and OrA-ir; conversely, the dendrites in the INF and the TM were non-immunoreactive. In these regions, OrA-ir terminals contained many small, clear, round vesicles with few large, dense core vesicles, suggesting that orexinergic neurons also provide excitatory input to other neurons in these regions.
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PMID:Orexin (hypocretin)-like immunoreactivity in the cat hypothalamus: a light and electron microscopic study. 1120 55

Orexins are expressed in neurons of the dorsolateral hypothalamus and their axons widely distribute throughout the central nervous system. The noradrenergic cell groups of the lower brainstem belong to the targets of these orexin projections. Double immunostainings for orexin and phenylethanolamine N-methyltransferase (PNMT), as well as orexin and tyrosine hydroxylase (TH) were applied to demonstrate the orexinergic innervation of catecholamine cell groups in the lower brainstem of the mouse and the rat. In various densities, networks of orexin-positive fibers and terminals were present on neurons of each adrenaline (C1, C2, C3) and noradrenaline (locus coeruleus, A1, A2, A4, A5 and A7) cell groups. The most dense networks of orexin fibers and terminals were detected in the locus coeruleus, the subcoeruleus area, and in the nucleus of the solitary tract. By using confocal microscope to analyze triple immunostainings we could detect that about two-third of the orexin-PNMT or orexin-TH immunopositive close contacts contained synaptophysin (a presynapse-specific protein) in the C1, C2 and C3 adrenaline, or in the A1, A2 noradrenaline cell groups, respectively. Orexin-immunopositive axons in the C1, C2, as well as A1, A2 and A6 cell groups have been examined by an electron microscope. Relatively few asymmetrical (excitatory) synaptic contacts could be demonstrated between PNMT- or TH-positive dendrites and orexin terminals, although the vast majority of orexin-positive axons was located in juxtaposition to PNMT- or TH-positive neurons.
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PMID:Interactions between orexin-immunoreactive fibers and adrenaline or noradrenaline-expressing neurons of the lower brainstem in rats and mice. 2043 98