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) has been shown to mediate refinement of glutamatergic axonal pathways during development. In this study, we investigated whether the development of a cholinergic pathway in the intermediate gray layer (IGL) of the mouse superior colliculus (SC) is also mediated by NO. The pathway was labeled using an antibody directed against choline acetyltransferase (ChAT) and its distribution examined in normal C57/BL6 mice and in knockout mice in which the genes for the neuronal isoform of nitric oxide synthase (NOS) or both the endothelial and neuronal isoforms of NOS had been disrupted. We also examined the development of expression of NOS using nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) staining. NADPHd labeled cells were found within the IGL by P8 and formed loose clusters of cells by P12-P15. ChAT and NADPHd labeled fibers were first observed at P12 and gradually established their characteristic two-tiered patchy pattern between P14 and P21. Comparison of the ChAT labeled fiber distribution in normal, single nNOS and double e,nNOS knockout mice revealed no differences between these three groups. We therefore conclude that nitric oxide does not mediate refinement of this cholinergic pathway.
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PMID:Failure to disrupt development of cholinergic fiber patches in the superior colliculus in nitric oxide synthase deficient mice. 1061 22

To understand the mechanisms leading to the progressive loss of intrinsic neuronal growth properties during central nervous system development, we have investigated the evolution of the response to injury and regenerative potential of immature Purkinje cells, axotomized at different postnatal ages from postnatal day (P)3 to P12. In adult rodents, these neurons are characterised by a weak cell body response to axotomy, which is associated with a remarkable resistance to injury and a poor regenerative capability. During the first postnatal week, Purkinje cells are strongly sensitive to injury and massively degenerate within a few days. Immature Purkinje cells react to neurite transection by a strong upregulation of c-Jun, accompanied by a moderate, but consistent, expression of the growth-associated protein (GAP)-43. In contrast, nicotinamide adenine dinucleotide monophosphate (NADPH)-diaphorase reactivity, which can be activated by adult Purkinje neurons, is not modified in their juvenile counterparts. The severed Purkinje axons show a vigorous regenerative sprouting both into the lesioned cerebellar environment and into embryonic neocortical tissue transplanted into the injury site. The typical adult features of the response to injury progressively develop during the second postnatal week, when the injured neurons acquire resistance, cell body changes become milder, the regenerative potential declines, and the severed axons undergo characteristic morphological modifications, including torpedoes and the hypertrophy of recurrent collateral branches. This complete reversal of the features and the outcome of the Purkinje cell reaction to axotomy likely results from the profound changes that occur in the maturing Purkinje cells and/or in their microenvironment during this phase of cerebellar development.
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PMID:Evolution of the Purkinje cell response to injury and regenerative potential during postnatal development of the rat cerebellum. 1113 48

The histochemical method was used to investigate the postnatal development of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) -positive neurons in retinas of the golden hamster. NADPH-d-positive neurons were discernible in the retina at postnatal day (P)1. From P4 onward to adulthood, when the retina acquired its laminated characteristics, NADPH-d- positive neurons were observed in the inner nuclear layer (INL) and the ganglion cell layer (GCL). Results showed that NADPH-d-positive neurons in INL and GCL followed different time courses and patterns in their development. NADPH-d-positive neurons in INL underwent a sharp increase from P4 to P8 (3.6-fold), followed by a decrease to 46% of the maximum at P12. This value was maintained relatively constant to the adult level. The mean diameters of NADPH-d-positive neurons in INL, which were smaller than those in the GCL for all ages, increased from P8 to P12 and from P20 to adulthood. As for neurons in the GCL, the increase in cell number was not so apparent for the earlier postnatal days until P20; thereafter, an obvious increase to the adult level was observed. The mean diameters of the NADPH-d-positive cell bodies in the GCL increased with age, except for P16-P20, during which time there was a slight and insignificant decrease. The tendency of changes in cell density was basically similar to that of the total number for both the INL and the GCL. Between P12 and P20, the density distribution map of the NADPH-d-positive neurons underwent dramatic changes: The highest density shifted from the upper central retina at the earlier postnatal days to the lower central retina in the adult. The two waves of increase in NADPH-d-positive neurons coincide with the process of axonal elongation and synaptogenesis and the acquisition of visual function and experience. It is suggested that these NADPH-d-positive neurons are related to these two developmental events.
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PMID:Postnatal development of nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in the retina of the golden hamster. 1195 33

Nitric oxide (NO) is a diffusible messenger molecule produced primarily by neuronal nitric oxide synthase (nNOS) in the central nervous system. Both nNOS expression and NO production are regulated by calcium ions. Leaner and tottering mice carry a mutation in the pore forming subunit (alpha1A) of P/Q-type voltage-gated calcium ion channels, which decreases calcium ion current through the affected channels and disrupts calcium homeostasis. We have previously shown that nNOS expression is altered in adult leaner and tottering cerebella. In addition, leaner and tottering mice have been shown to have abnormal cerebellar granule cell-Purkinje cell synapses and leaner cerebellar granule cells undergo abnormal apoptosis during early postnatal development. Since NO production has been linked to several developmental roles including neuronal cell death, synaptogenesis and neuronal cell survival, our objective was to evaluate the expression of nNOS in developing leaner and tottering cerebella. Our results show that nNOS is differentially expressed in leaner and tottering cerebella compared to wild type cerebella and compared to each other. In whole cerebella, Western blotting revealed a significant increase in nNOS expression at postnatal day 12 in tottering but not leaner or wild type cerebella. At the cellular level the NADPH-diaphorase marker for nNOS revealed a significant increase in nNOS expression in basket cell interneurons in both mutant mice. nNOS expression in granule cells in the internal granule cell layer in tottering mice was increased at P12, while granule cells of leaner mice exhibited decreased nNOS expression at P20. The changes in nNOS expression at P12 did not correlate with a change in overall NO production, but rather maintained wild type NO concentrations. These findings suggest that changes in nNOS expression in the leaner and tottering cerebella are compensatory in nature with NO most likely functioning as a calcium-regulated neuroprotective/neurotrophic factor in postnatal cerebellar development.
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PMID:Developmental expression of neuronal nitric oxide synthase in P/Q-type voltage-gated calcium ion channel mutant mice, leaner and tottering. 1635 45

Nicotinamide Adenine Dinucleotide Phosphate-Diaphorase (NADPH-d) expressing neurons in the retina of golden hamsters have been identified to be a subset of amacrine cells that provide a major source of Nitric Oxide (NO) in retina. This subset of amacrine cells in mouse retina was recently proved to contain the circadian clock gene Per1 (D.Q. Zhang, T. Zhou, G.X. Ruan, D.G. McMahon, Circadian rhythm of Period 1 clock gene expression in NOS amacrine cells of the mouse retina, Brain Res., 1050 (2005) 101-109). However, it remains unknown whether these clock-related NADPH-d amacrine cells can be regulated by light stimulation and thus synchronized to ambient day/night cycle. A previous study has reported that NADPH-d expressing amacrine cells in postnatal hamsters exhibited a surge after eye-opening (D. Tay, Y.C. Diao, Y.M. Xiao, K.F. So, Postnatal development of nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in the retina of the golden hamster, J. Comp. Neurol., 446 (2002) 342-348) suggesting a possible effect of light on the NADPH-d amacrine cells. In order to further reveal the relationship between NADPH-d amacrine cells and light stimulation, the present study focuses on the changes of the expression of NADPH-d in the retina of postnatal hamsters reared in completely deprived light conditions. Prior to eye opening, P12 hamster pups were subjected to either bilateral eyelid suturing or dark rearing. On P28 a subgroup of light deprived hamsters was returned to lighting conditions and the expression of NADPH-d activities in the retina was assessed. In hamsters reared in the 12:12 light-dark cycle, the number of NADPH-d amacrine cells in the ganglion cell layer (GCL) increased right after eye-opening and reached the adult level gradually. However, hamsters subjected to both bilateral eyelid suturing and dark rearing, the number of NADPH-d amacrine cells in GCL was maintained at a low level but increased again upon returning to the 12:12 light-dark condition. In contrast, the number of NADPH-d expressing amacrine cells in the inner nuclear layer (INL) remained low and unaltered regardless of the lighting environment. This study demonstrates that there are two subpopulations of NADPH-d expressing amacrine cells with respect to different locations in the retina of hamsters. Different from those in INL, the NADPH-d amacrine cells in GCL of postnatal hamsters are dependent on the lighting environment implicating that these clock-related amacrine cells and the production of NO might be under a modulation of light stimulation.
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PMID:Expression of nicotinamide adenine dinucleotide phosphate-diaphorase in the retina of postnatal golden hamsters deprived of light stimulation. 1685 23

We have studied the development of NADPH-diaphorase activity in the retinorecipient layers of the superior colliculus (SC) in rats from embryonic day 17 to adulthood, during aging, and following neonatal tetrodotoxin injection or unilateral eye removal in the neonatal or in the adult animal. In the superficial SC, NADPH-d activity is first seen in neurons on postnatal day (P) 4; over the next two weeks, enzyme expression increases gradually, in cells as well as in the neuropil. By P12-14, around the time of eye opening, NADPH-d reactivity increases dramatically. In parallel, the dendrites of many NADPH-d-positive neurons in the superficial gray layer, more or less randomly distributed at first, gradually align their orientation relative to the dorsoventral axis. The pattern of NADPH-d activity in the superficial layers of the SC (i.e. stratum griseum superficiale and stratum opticum) is adult-like by the fourth week of age. Deafferentation of the superficial SC, both in the neonatal and adult rat, and block of retinal activity lead to reduction in the size of the SC and changes in NADPH-d-positive neurons, including dendrite misorientation, decreased cell size and reduced number. Some of these changes are seen also in the aging animal. These results document a protracted and progressive increase in the development of NADPH-d expression in the SC. Our results suggest a strong influence of retinal afferents and activity on the development and maintenance of NAPHD-positive neurons in the retinorecipient layers of the SC, where NO can act as a retrograde signal to carve the terminal arbors of retinal axons.
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PMID:NADPH diaphorase expression in superior colliculus of developing, aging and visually deafferented rats. 2342 Sep 45