Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orexin-A and -B are recently identified potent orexigenic peptides that are derived from the same precursor peptide and are highly specifically localized in neurons located in the lateral hypothalamic area, a region classically implicated in feeding behavior. We cloned the whole length of the human prepro-orexin gene and corresponding cDNA. The human prepro-orexin mRNA was predicted to encode a 131-residue precursor peptide (prepro-orexin). The human prepro-orexin gene consists of two exons and one intron distributed over 1432 base pairs. The 143-base pair first exon includes the 5'-untranslated region and a small part of the coding region that encodes the first seven residues of the secretory signal sequence. The second exon contains the remaining portion of the open reading frame and 3'-untranslated region. The 3.2 kilobase pairs of the 5'-upstream region from a cloned human prepro-orexin gene promoter is sufficient to direct the expression of the Escherichia coli beta-galactosidase (lacZ) gene in transgenic mice to neurons in the lateral hypothalamic area and adjacent regions. The lacZ-positive neurons were positively stained with anti-orexin antibody but not with anti-melanin-concentrating hormone antibody. These findings suggest that this genomic fragment contains all the necessary elements for appropriate expression of the gene and will be useful for the targeted expression of the exogenous gene in orexin-containing neurons. These mice might also be useful for examining the molecular mechanisms by which orexin gene expression is regulated.
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PMID:Structure and function of human prepro-orexin gene. 1036 20

Two anatomical experiments were performed to test the hypothesis that single CNS neurons link the central areas that regulate the somatomotor and sympathetic systems. First, the retrograde neuronal tracer cholera toxin beta-subunit was injected into the lateral parafascicular thalamic nucleus, a region that projects to both the motor cortex and striatum. Several days later, a second injection of the retrograde transneuronal tracer, pseudorabies virus (PRV), was made in the same rats in the stellate ganglion, which provides the main sympathetic supply to the heart. Using immunohistochemical methods, we demonstrate that the cholinergic neurons of the pedunculopontine tegmental nucleus (PPN) are connected to both systems. The second experiment used two isogenic strains of Bartha PRV as double transneuronal tracers. One virus contained the unique gene for green fluorescent protein (GFP) and the other had the unique gene for beta-galactosidase (beta-gal). GFP-PRV was injected in the stellate ganglion and beta-gal-PRV was injected into the primary motor cortex. Double-labeled neurons were found in the lateral hypothalamic area (50% contained orexin) and PPN (approximately 95% were cholinergic). Other double-labeled neurons were identified in the deep temporal lobe (viz., amygdalohippocampal zone and lateral entorhinal cortex), posterior hypothalamus, ventral tuberomammillary nucleus, locus coeruleus, laterodorsal tegmental nucleus, periaqueductal gray matter, dorsal raphe nucleus, and nucleus tractus solitarius. These results suggest these putative command neurons integrate the somatomotor and cardiosympathetic functions and may affect different behaviors (viz., arousal, sleep, and/or locomotion).
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PMID:Single CNS neurons link both central motor and cardiosympathetic systems: a double-virus tracing study. 1271 Sep 92

Neuropeptide Y (NPY)-expressing neurones in the arcuate nucleus densely innervate many hypothalamic nuclei. To determine the neurochemical phenotype of target neurones for NPY, we studied the immunohistochemical localization of the NPY Y1 receptor (Y1R) in discrete subpopulations of neurones in the rat hypothalamus. Among several tested populations, including hypocretin/orexin-, melanin-concentrating hormone (MCH)- and nitric oxide synthase (NOS)-positive neurones, only the latter were found to coexpress the Y1R. Numerous Y1R/NOS-positive neurones were found as a densely packaged group of cells located ventrolateral to the ventromedial nucleus, forming a band ascending towards the fornix. Lower numbers of Y1R/NOS-positive neurones were found in the perifornical area and in the peri- and paraventricular nuclei. Expression of the Y1R gene was found in the same locations in the mouse by colocalizing beta-galactosidase, a Y1R gene reporter, with NOS in a Y1R knockout mouse. To explore possible downstream targets of NO in the rat hypothalamus, the NO-regulated molecule cGMP was analysed immunohistochemically after incubation of brain slices with sodium nitroprusside, an NO donor. We observed several cGMP-positive cell bodies in the arcuate nucleus, cGMP-positive blood vessels and a cGMP-positive network of thin fibres, some of which colocalized with choline acetyltransferase.
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PMID:Neuropeptide y targets in the hypothalamus: nitric oxide synthesizing neurones express Y1 receptor. 1283 36

Orexin and melanin-concentrating hormone (MCH) have been implicated in mediating a variety of different behaviors. These include sleep and wakefulness, locomotion, ingestive behaviors, and fight-or-flight response, as well as anxiety- and panic-like behaviors in rodents. Despite such diversity, all these processes require coordinated recruitment of the autonomic and somatomotor efferents. We have previously mapped the locations of presympathetic-premotor neurons (PSPMNs) in the rat brain. These putative dual-function neurons send trans-synaptic projections to somatomotor and sympathetic targets and likely participate in somatomotor-sympathetic integration. A significant portion of these neurons is found within the dorsomedial (DMH) and lateral hypothalamus (LH), areas of the brain that contain MCH- and orexin- synthesizing neurons in the central nervous system. Thus, we hypothesized that hypothalamic PSPMNs utilize MCH or orexin as their neurotransmitter. To test this hypothesis, we identified PSPMNs by using recombinant strains of the pseudorabies virus (PRV) for trans-synaptic tract tracing. PRV-152, a strain that expresses enhanced green fluorescent protein, was injected into sympathectomized gastrocnemius muscle, whereas PRV-BaBlu, which expresses beta-galactosidase, was injected into the adrenal gland in the same animals. By using immunofluorescent methods, we determined whether co-infected neurons express MCH or orexin. Our findings demonstrate that PSPMNs synthesizing either MCH or orexin are present within LH, where they form two separate populations. PSPMNs located around the fornix express orexin, whereas those located around the cerebral peduncle are more likely to express MCH. These two clusters of PSPMNs within LH likely play distinct functional roles in autonomic homeostasis and stress coping mechanisms.
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PMID:Distinct populations of presympathetic-premotor neurons express orexin or melanin-concentrating hormone in the rat lateral hypothalamus. 1792 41