Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO), a simple gas with free radical chemical properties, is synthesized by nitric oxide synthase (NOS) from arginine in neurons and acts as a neurotransmitter in the central and peripheral nervous systems. The immunohistochemical demonstration of NOS-immunoreactivity and its histochemical marker, NADPH-diaphorase activity in many neurons of the hypothalamus, suggest that NO plays a role in controlling the production and/or release of hypothalamic neuroendocrine peptides. In the present study, the expression of NOS in the enkephalin and dynorphin systems of the rat hypothalamus was examined by the combined method of the NADPH-diaphorase histochemistry and the immunocytochemistry of methionine enkephalin (M-Enk) or dynorphin B (Dyn-B). About 6 to 9% of M-Enk immunoreactive neurons in the paraventricular, arcuate and ventromedial nuclei expressed NADPH-diaphorase activity. Dyn-B immunoreactive neurons, however, showed NADPH-diaphorase activity in high ratio (37%-84%) in the supraoptic nucleus and the parvocellular and magnocellular paraventricular nucleus. These results revealed that a part of the enkephalin and dynorphin neurons in the rat hypothalamus have the ability to produce NO. The high ratio of expression of NO in magnocellular neurosecretory dynorphin containing neurons suggested that NO participates in controlling posterior pituitary hormone secretion together with dynorphin.
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PMID:[Expression of nitric oxide synthase in enkephalin and dynorphin systems of the rat hypothalamus]. 752 49

Substance P immunoreactivity is localized in discrete subsets of neurons in the human cerebral cortex and basal ganglia. In the normal human cerebral cortex, a subset of aspiny local circuit neurons in deep cortical layers and the cortical subplate contain preprotachykinin mRNA and substance P immunoreactive. These neurons, which contain NADPH diaphorase (NO synthase) activity, are strikingly depleted in Alzheimer's disease--in contrast to other local circuit neurons--suggesting that they may be an early target of the degenerative process. In the human basal ganglia, substance P immunoreactivity and mRNA are localized in a subset of spiny striatal neurons that project to the internal segment of the globus pallidus. These neurons are enriched in D1 dopamine receptors and dynorphin, and are calbindin and DARP 32 immunoreactive. A separate subset of aspiny striatal local circuit neurons also contain substance P immunoreactivity. Fiber and terminal staining is prominent in the matrix compartment of the ventromedial striatum and persists dorsally as a rim outlining patches that contain lesser amounts of immunoreactivity. Intense fiber and terminal staining is found in the pars reticulata of the substantia nigra. In Huntington's disease, substance P is depleted in the striatum in parallel with the dorsoventral gradient of neuronal loss. Terminal staining is progressively depleted in the pallidum and substantia nigra in tandem with striatal atrophy. Substance P receptor immunoreactivity, defined with two polyclonal antisera raised against synthetic peptides derived from the substance P receptor sequence, intensely labels a subset of large neurons in the nucleus basalis and striatum identical to neurons labeled with choline acetyltransferase and nerve growth factor receptor antibodies (although striatal cholinergic neurons do not contain nerve growth factor receptor immunoreactivity in the human). These cholinergic neurons resist degeneration in Huntington's disease but are sensitive to degeneration in Alzheimer's disease. Less intensely labeled neurons include pyramidal neurons in the hippocampal CA2 field, nonpyramidal neurons in CA1-4, pyramidal and nonpyramidal neurons in deep neocortical layers and in the cortical subplate. Substance P receptor immunoreactivity is not well defined in the human globus pallidus or substantia nigra.
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PMID:Substance P and substance P receptor histochemistry in human neurodegenerative diseases. 769 86

Neurons in the human adrenal medulla, stained by the NADH-diaphorase reaction, were counted and their neurochemical markers were investigated by double labeling immunofluorescence with special reference to substance P. The findings indicate a significant participation of intramedullary nerve cell bodies in human adrenal innervation with 40.4 neurons/mm3 adrenal medulla. Substance P-immunoreactive neurons, which made up approximately 20% of all neurons, exhibited heterogeneity by co-localization of immunoreactivities for dynorphin, for cholecystokinin, and for neurofilament triplet. Substance-P-immunolabeled neurons were always nonreactive for calcitonin gene-related peptide, for vasoactive intestinal polypeptide, or for tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis. These chemical phenotypes of intramedullary neurons reveal immunohistochemical similarities with postganglionic neurons in parasympathetic ganglia or with enteric neurons, suggesting a hitherto unrecognized functional significance of the intrinsic nervous system in the human adrenal gland.
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PMID:Immunohistochemical heterogeneity of nerve cells in the human adrenal gland with special reference to substance P. 860 96

Nitric oxide (NO) mediation in the spinal cord injury induced by intrathecal (i.t.) dynorphin (Dyn) administration was studied with NADPH-diaphorase (Nd) histochemistry. Normally, there was rarely NO synthase (NOS) activity in spinal cord motomeurons, and Dyn A(1-17) 10 nmol, which produced only transient paralysis, did not induce Nd/NOS expression in ventral horn cells. After a paralyzing dose of i.t. Dyn A(1-17) 20 nmol, which definitely produced permanent paraplegia and neuronal death, Nd/NOS began to express in motoneurons at 30 min, increased in numbers and intensities at 2-4 h and persisted up to 8 h. Most of Nd/NOS motoneurons disappeared at 24 h coincident with the neuronal death. Quite a few intensively-stained Nd-positive small cells and swollen varicosities became visible only in rats with permanent paraplegia and neuronal death, beginning at 2 h, maximizing at 3-4 h and remaining up to 24 h. These results suggest that NOS expression was induced in the ventral horn of spinal cord, including small cells and varicosities as well as motoneurons closely correlated in time and degree with pathological changes in motoneurons caused by spinal Dyn neurotoxicity.
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PMID:Dynorphin neurotoxicity induced nitric oxide synthase expression in ventral horn cells of rat spinal cord. 874 35

The neocortex is thought to exert a powerful influence over the functions of the basal ganglia via its projection to the striatum. It is not known, however, whether corticostriatal effects are similar across different types of striatal projection neurons and interneurons or are unique for cells having different functions within striatal networks. To examine this question, we developed a method for focal synchronous activation of the primary motor cortex (MI) of freely moving rats by local release of GABAergic inhibition. With this method, we monitored cortically evoked activation of two immediate-early gene protein products, c-Fos and JunB, in phenotypically identified striatal neurons. We further studied the influence of glutamate receptor antagonists on the stimulated expression of c-Fos, JunB, FosB, and NGFI-A. Local disinhibition of MI elicited remarkably selective induction of c-Fos and JunB in enkephalinergic projection neurons. These indirect pathway neurons, through their projections to the globus pallidus, can inhibit thalamocortical motor circuits. The dynorphin-containing projection neurons of the direct pathway, with opposite effects on the thalamocortical circuits, showed very little induction of c-Fos or JunB. The gene response of striatal interneurons was also highly selective, affecting principally parvalbumin- and NADPH diaphorase-expressing interneurons. The glutamate NMDA receptor antagonist MK-801 strongly reduced the cortically evoked striatal gene expression in all cell types for each gene examined. Because the gene induction that we found followed known corticostriatal somatotopy, was dose-dependent, and was selectively sensitive to glutamate receptor antagonists, we suggest that the differential activation patterns reflect functional specialization of cortical inputs to the direct and indirect pathways of the basal ganglia and functional plasticity within these circuits.
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PMID:Local release of GABAergic inhibition in the motor cortex induces immediate-early gene expression in indirect pathway neurons of the striatum. 916 35

The aim of the present study was to analyze the neurochemical properties of the centrifugal visual system (CVS) of the quail using an immunohistochemical approach by testing 16 neuropeptides (angiotensin: ANG, bradykinin: BK, cholecystokinin, dynorphin, L and M-enkephalin, beta-endorphin: beta-END, galanin, alpha-neoendorphin, neurokinin A, neuropeptide Y (NPY), ocytocin, somatostatin, substance P, vasopressin, vasoactive intestinal polypeptide) and three neurotransmitters or their synthetic enzymes (choline acetyltransferase: ChAT, tyrosine hydroxylase: TH, serotonin: 5-HT and nitric oxide synthase: NOS, including the histochemical nicotinamide adenine dinucleotide phosphate diaphorase technique). For each substance, the somatic and afferent fiber and terminal labeling was analyzed within the nucleus isthmo-opticus (NIO) and the ectopic area (EA) and compared with that of retinopetal cell bodies labeled retrogradely with RITC following its intraocular injection (double-labeling procedure). The results showed that none of the centrifugal neurons were reactive to any of the substances tested. In contrast, all with the exception of ANG, BK and beta-END, labeled fibers and terminals within the EA and only four (ChAT, 5-HT, NPY and NOS) within the NIO. Possible sources of these immunoreactive fibers terminating in the NIO and EA were investigated by mapping the somatic immunolabeling of the different substances within brainstem regions previously shown by Miceli and other authors to project upon the centrifugal neurons. The data suggests that, besides the rapid retino-tecto-NIO-retinal loop, which facilitates the transfer of meaningful or more relevant information within particular portions of the visual field, the multiple afferent input which stems from various brainstem regions utilizes a wide range of neuroactive substances. Some of these afferent projections upon the centrifugal neurons appear to belong to nonspecific systems which might play a role in modulating the excitability of centrifugal neurons as a function of arousal.
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PMID:An immunohistochemical study of putative neuromodulators and transmitters in the centrifugal visual system of the quail (Coturnix japonica). 971 61

This study was carried out in order to examine the effects of acute or chronic L-DOPA treatment on striatally expressed FosB- and JunB-like proteins in a rat model of Parkinson's disease. Rats with a unilateral, near-total 6-hydroxydopamine lesion of the ascending mesostriatal projection received either an acute challenge or a one-week treatment with 10 mg/kg/day methyl L-DOPA (combined with 15 mg/mg benserazide), and were killed at either 3 h or two days post-injection. Both acute and chronic L-DOPA treatment caused a pronounced, persistent increase in the number of FosB-like immunoreactive cells in the dopamine-denervated striata (five- and seven-fold increase, respectively, above the levels found in lesioned but non-drug-treated controls), but the two treatment groups differed markedly with respect to both the average amount of staining per cell, which was two-fold larger in the chronic L-DOPA cases, and the anatomical distribution of the labeled cells. After an acute injection of L-DOPA, FosB-positive cells were distributed rather uniformly across all striatal subregions, whereas chronic L-DOPA treatment induced discrete clusters of strongly FosB-like immunoreactive cells within medial and central striatal subregions, as well as in a large, yet sharply defined portion of the lateral caudate-putamen. Strongly labeled cell clusters that appeared in the medial and central caudate-putamen were preferentially located within calbindin-poor, mu-opioid receptor-rich striosomes, whereas the lateral area displaying FosB activation encompassed both striosomal and matrix domains. In both the medial and the lateral striatum a near-total overlap was found between strongly FosB-like immunoreactive cell groups and areas showing pronounced dynorphin expression. NADPH-diaphorase-positive striatal interneurons did not express FosB-like immunoreactivity after a 6-hydroxydopamine lesion alone, a negligible proportion of them did after an acute L-DOPA challenge, but about 8% of these interneurons were FosB positive following chronic L-DOPA treatment. Like FosB, JunB was induced in the DA-denervated striatum by both acute and chronic L-DOPA treatment, and exhibited similar distribution patterns. However, JunB did not exhibit prolonged expression kinetics, and was somewhat down-regulated in the chronically compared with the acutely L-DOPA-treated rats. The present results show that L-DOPA administration produces a long-lasting increase in the levels of FosB-, but not JunB-like immunoreactivity in the dopamine-denervated striatum. More importantly, these data show that striatal induction of FosB- and JunB-like proteins by chronic L-DOPA treatment exhibits both regional and compartmental specificity.
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PMID:Changes in the regional and compartmental distribution of FosB- and JunB-like immunoreactivity induced in the dopamine-denervated rat striatum by acute or chronic L-dopa treatment. 1057 13

To test for the relative contributions of the dopaminergic and serotoninergic systems in the striatum to the effects of d-fenfluramine, an indirect serotonin receptor agonist, we assessed the expression of Fos/Jun proteins induced by d-fenfluramine given alone or in the presence of dopaminergic or serotoninergic agents. To determine the neuronal targets of d-fenfluramine in the striatum, we identified the phenotypes of striatal neurons in which d-fenfluramine induced Fos expression. Our results demonstrated that d-fenfluramine evokes nuclear expression of Fos/Jun B proteins in the striatum, and that the Fos expression was dose-dependent and accompanied by transient induction of c-fos mRNA. Fos expression was blocked by p-chloroamphetamine, a serotoninergic neurotoxin. Pretreatment with SCH 23390, a D1-dopamine receptor antagonist, led to a marked decrease in Fos/Jun B expression in the caudoputamen, but not in the cortex, whereas pretreatment with methiothepin, a nonselective serotonin 5-HT1 receptor antagonist, blocked Fos expression completely in the cortex and only partially in the caudoputamen. The expression of Fos/Jun B in the striatum occurred mainly in dynorphin-containing neurons and in a subpopulation of striatal interneurons that exhibited NADPH-diaphorase activity. Most of the enkephalin-containing neurons of the striatum did not show Fos/Jun B staining. These results suggest that the mechanism by which d-fenfluramine induces c-fos and jun B expression in the rat caudoputamen depends at least in part on activation of the dopaminergic system by serotonin.
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PMID:Interaction between the serotoninergic and dopaminergic systems in d-fenfluramine-induced activation of c-fos and jun B genes in rat striatal neurons. 1073 91

A new subdivision, the "marginal division" (MrD), was discovered at the caudal border of the striatum and surrounds the rostral edge of the globus pallidus in the rat brain in our previous studies. The neuronal somata of the MrD are mostly fusiform in shape with their long axes lining dorsoventrally. The MrD is more densely filled with substance P (SP)-, Leucine-enkephalin (L-Enk)-, dynorphin B-, neurotensin-, somatostatin- and cholecystokinin (CCK)-immunoreactive fibers and terminal-like structures than the rest of the striatum. The MrD was confirmed in the cat neostriatum as well. The present study intended to explore whether the MrD exists in the monkey neostriatum (putamen) with Nissl, histochemical and immunohistochemical methods. A band of fusiform neurons were obviously identified at the caudomedial edge of the putamen. These neurons lie outside the lateral medullary lamina and indirectly surround the rostrolateral border of the globus pallidus. The abundance of SP-, L-Enk-, neuropeptide Y-, CCK-, dopamine- and serotonin-positive fibers and terminal-like structures with a few positive fusiform neurons accumulating at the caudomedial border of the putamen obviously distinguishes this zone from the rest of neostriatum and globus pallidus. The acetylcholinesterase (AChE) positive and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) containing fusiform neurons are distinctly visualized in the same zone. The morphological figure and the location of these neurons, and the histochemical and immunohistochemical characteristics of this area coincide well with those of the MrD in the rat and cat striatum. This study thus convincingly identifies the existence of the MrD in the monkey neostriatum. It is fairly asserted that the MrD is a universal structure in the mammalian brain.
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PMID:A new subdivision, marginal division, in the neostriatum of the monkey brain. 1078 7

The different types of striatal neuron show a range of vulnerabilities to a variety of insults. This can be clearly seen in Huntington's disease where a well mapped pattern of pathological events occurs. Medium spiny projection (MSP) neurons are the first striatal cells to be affected as the disease progresses whilst interneurons, in particular the NADPH diaphorase positive ones, are spared even in the late stages of the disease. The MSP neurons themselves are also differentially affected. The death of MSP neurons in the patch compartment of the striatum precedes that in the matrix compartment and the MSP neurons of the dorsomedial caudate nucleus degenerate before those in the ventral lateral putamen. The enkephalin positive striatopallidal MSP neurons are also more vulnerable than the substance P/dynorphin MSP neurons. We review the potential causes of this selective vulnerability of striatopallidal neurons and discuss the roles of endogenous glutamate, nitric oxide and calcium binding proteins. It is concluded that MSP neurons in general are especially susceptible to disruptions of cellular respiration due to the enormous amount of energy they expend on maintaining unusually high transmembrane potentials. We go on to consider a subpopulation of enkephalinergic striatopallidal neurons in the rat which are particularly vulnerable. This subpopulation of neurons readily undergo apoptosis in response to experimental manipulations which affect dopamine and/or corticosteroid levels. We speculate that the cellular mechanisms underlying this cell death may also operate in degenerative disorders such as Huntington's disease thereby imposing an additional level of selectivity on the pattern of degeneration. The possible contribution of the selective death of striatopallidal neurons to a number of clinically important psychiatric conditions including obsessive compulsive disorders and Tourette's syndrome is also discussed.
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PMID:The selective vulnerability of striatopallidal neurons. 1084 58


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