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)

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.
 ...
PMID:Substance P and substance P receptor histochemistry in human neurodegenerative diseases. 769 86

In this study, enteric nervous system (ENS) of the fetal intestinal grafts was examined histopathologically. Forty-four rat fetal small intestines were transplanted syngenetically into the subcutaneous region of adult rats without vascular anastomosis. Thirty-two grafts survived. They were removed 2, 4, 6, and 8 weeks after transplantation and examined using (1) H&E staining, (2) AChE and NADPH-diaphorase histochemistry, and (3) protein gene product 9.5, S-100 protein, glial fibrillary acidic protein, tyrosine hydroxylase, nerve growth factor receptor, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal peptide, somatostatin, and substance P immunohistochemistry. The grafts were compared with the intestines of 2-, 4-, 6- and 8-week-old control rats. ENS of the grafts was different from the controls as follows: (1) tyrosine hydroxylase and neuropeptide Y were markedly reduced but present, suggesting that the extrinsic innervation was present; (2) nitric oxide-producing neurons were well preserved in grafts; (3) hyperganglionosis in the myenteric plexus was seen in 6- and 8-week grafts; (4) AChE activity was increased in the circular muscle and in the lamina propria, (5) S-100 was increased in the lamina propria in 6- and 8-week grafts, (6) calcitonin gene-related peptide was increased in 6- and 8-week grafts, (7) nerve fibers in the muscle layers ran irregularly and disorderly, and (8) hypertrophy of smooth muscle layers. Our data show that although extrinsic as well as intrinsic innervation is present in the fetal intestinal grafts, there is hyperinnervation of the intrinsic nervous system and reduced innervation of the extrinsic ENS. These morphological changes in the ENS of the fetal intestinal grafts may result in motility dysfunction.
 ...
PMID:Morphological changes in the enteric nervous system of the transplanted fetal rat intestine. 920 96

The small magnocellular group located within the rostrolateral extension of the basal forebrain was named and described as the nucleus subputaminalis in the human and chimpanzee brain by Ayala. Analysis of cytoarchitectonic and cytochemical characteristics of this cell group has been largely disregarded in both classical and more current studies. We examined the nucleus subputaminalis in 33 neurologically normal subjects (ranging from 15 weeks of gestation to 71 years-of-age) by using Nissl staining, choline acetyltransferase immunohistochemistry, acetyl cholinesterase histochemistry and nerve growth factor receptor immunocytochemistry. In addition, we applied reduced nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry and calbindin-D28k immunocytochemistry in three neurologically normal subjects. At the most rostrolateral levels we describe the previously poorly characterized component of the lateral (periputaminal) subdivision of the subputaminal nucleus, which may be human specific since it is not described in non-human primates. Moreover, we find the human subputaminal nucleus best developed at the anterointermediate level, which is the part of the basal nucleus that is usually much smaller or missing in monkeys. The location of subputaminal cholinergic neurons within the frontal lobe, the ascension of their fibers through the external capsule towards the inferior frontal gyrus, the larger size of the subputaminal nucleus on the left side at the most rostral and anterointermediate levels and the most protracted development among all magnocellular aggregations within the basal forebrain strongly suggest that they may be connected with the cortical speech area. These findings give rise to many hypotheses about the possible role of the subputaminal nucleus in various neurodegenerative, neurological and psychiatric disorders, particularly Alzheimer's disease and primary progressive aphasia. Therefore, future studies on the basal forebrain should more carefully investigate this part of the basal nucleus.
 ...
PMID:Nucleus subputaminalis (Ayala): the still disregarded magnocellular component of the basal forebrain may be human specific and connected with the cortical speech area. 1005 Dec 18

The enteric nervous system (ENS) poses the intrinsic innervation of the gastrointestinal tract and plays a critical role for all stages of postnatal life. There is increasing scientific and clinical interest in acquired or age-related gastrointestinal dysfunctions that can be manifested in diseases such as gut constipation or fecal incontinence. In this study, we sought to analyze age-dependent changes in the gene expression profile of the human ENS, particularly in the myenteric plexus. Therefore, we used the laser microdissection technique which has been proven as a feasible tool to analyze distinct cell populations within heterogeneously composed tissues. Full biopsy gut samples were prepared from children (4-12 months), middle aged (48-58 years) and aged donors (70-95 years). Cryosections were histologically stained with H&E, the ganglia of the myenteric plexus identified and RNA isolated using laser microdissection technique. Quantitative PCR was performed for selected neural genes, neurotransmitters and receptors. Data were confirmed on protein level using NADPH-diaphorase staining and immunohistochemistry. As result, we demonstrate age-associated alterations in site-specific gene expression pattern of the ENS. Thus, in the adult and aged distal parts of the colon a marked decrease in relative gene expression of neural key genes like NGFR, RET, NOS1 and a concurrent increase of CHAT were observed. Further, we detected notable regional differences of RET, CHAT, TH, and S100B comparing gene expression in aged proximal and distal colon. Interestingly, markers indicating cellular senescence or oxidative stress (SNCA, CASP3, CAT, SOD2, and TERT) were largely unchanged within the ENS. For the first time, our study also describes the age-dependent expression pattern of all major sodium channels within the ENS. Our results are in line with previous studies showing spatio-temporal differences within the mammalian ENS.
...
PMID:Age-related gene expression analysis in enteric ganglia of human colon after laser microdissection. 2536 Jan 10