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)

The alteration of certain neuropeptide levels is a dramatic and consistent finding in the brains of AD patients. Levels of SS, which is normally present in high concentrations in cerebral cortex /75/, are consistently decreased in the neocortex, hippocampus and CSF of AD patients. In addition, decreased levels of SS correlate regionally with the distribution of neurofibrillary tangles in AD /47/. Most available evidence suggests that the subset of SS-containing neurons which lack NADPH diaphorase may be relatively vulnerable to degeneration in AD. CRF is another neuropeptide with frequently observed changes in AD. Levels of CRF, which is normally present in low concentrations in cortical structures /75/, are decreased in the neocortex and hippocampus of AD patients. However, levels of CRF in the CSF of AD patients are not consistently reduced, but this is likely a reflection of the relatively low levels of CRF normally present in cerebral cortex. Studies of deep gray structures in AD brains reveal elevated levels of GAL in the nucleus basalis. The ability of GAL to inhibit cholinergic neurotransmission has generated considerable interest, since degeneration of cholinergic neurons in the basal forebrain consistently occurs in AD. In addition, the presence of NADPH diaphorase in GAL-containing neurons may underlie the relative resistance of these neurons to degeneration. From the aforementioned studies, it appears that the neurons which are relatively resistant to neurodegeneration in AD contain NADPH diaphorase. It is hypothesized that the presence of NADPH diaphorase protects these neurons from neurotoxicity mediated by glutamate or nitric oxide. Although one recent study /147/ has reported an elevation of the microtubule-associated protein tau in the CSF of AD patients (and this could become a useful antemortem diagnostic tool for AD), no similar CSF abnormality has been found for any of the neuropeptides. Thus, the measurement of CSF neuropeptide levels presently remains unhelpful in the diagnosis and treatment of AD. Future research on neuropeptides and their potential roles in the pathogenesis, diagnosis, and treatment of AD will likely involve further development of pharmacological modulators of neuropeptide systems, together with the further study of brain neuropeptidases.
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PMID:Neuropeptide changes in cortical and deep gray structures in Alzheimer's disease. 884 72

We investigated the chemical and anatomical features of nitric oxide synthase (NOS)-containing neurons in the paraventricular and supraoptic nuclei in the rat hypothalamus using combinations of enzyme histochemistry, in situ hybridization and immuno-histochemistry. Neurons expressing NOS mRNA completely overlapped with NADPH-diaphorase-positive neurons. Topographical distribution of NOS was segregated from that of CRF-containing parvicellular neurons in the posterior paraventricular nucleus but overlapped with that of magnocellular neurons. In the paraventricular nucleus, 70% of oxytocin neurons contained NOS, which corresponded to one half of NOS neurons. About one third of vasopressin-immunoreactive neurons were NADPH-diaphorase-positive and the same proportion of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. In the supraoptic nucleus, 50% of oxytocin neurons were NADPH-diaphorase-positive, which corresponded to 40% of NOS neurons. About 25% of vasopressin neurons were NADPH-diaphorase-positive, and 30% of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. When NADPH-diaphorase histochemistry was performed first, subsequent immunostaining was markedly perturbed. Using fluoro-gold as a retrograde tracer, 4% of NADPH-diaphorase-positive neurons were shown to contribute to the descending projection to the spinal cord. About 40%-50% of NADPH-diaphorase-positive neurons exhibited Fos immunoreactivity after injection of lipopolysaccharide or hypertonic saline, while only 10%-15% of these neurons expressed Fos in response to immobilization or pain. Endogenous NO may be involved in the regulation of magnocellular functions, especially when the internal environment is disturbed.
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PMID:Nitric oxide synthase-containing magnocellular neurons of the rat hypothalamus synthesize oxytocin and vasopressin and express Fos following stress stimuli. 895 94

Nitric oxide (NO) is known to be involved in the modulation of neuroendocrine function. To clarify the role of different isoforms of NO synthase (NOS) in the neuroendocrine response to immune challenge, the expressions of neuronal NOS (nNOS) and inducible NOS (iNOS) genes in the hypothalamus following lipopolysaccharide (LPS) injection were examined using in situ hybridization. NOS activity was also determined by NADPH-diaphorase (NADPH-d) histochemistry. LPS (25 mg/kg) or sterile saline was injected intraperitoneally to male Wistar rats and the rats sacrificed 30 min, or 1, 2, 3, 5, 12 or 24 h after injection. nNOS mRNA expression in the paraventricular nucleus (PVN) was significantly increased 2 h after LPS injection. iNOS mRNA, which was not detected until 2 h after LPS injection, was significantly increased in the PVN 3 h after LPS injection. Both RNA expressions had returned to basal levels by 12 h after LPS injection. The number of NADPH-d positive cells was significantly increased 5 h after LPS injection. iNOS expression was more robust in parvocellular PVN, while nNOS was distributed mainly in the magnocellular PVN. Double in situ hybridization histochemistry revealed that some of the iNOS- (48.4%) or nNOS-positive cells (34. 3%) in the parvocellular PVN expressed CRF mRNA. The results demonstrate that LPS-induced sepsis causes significant increases in nNOS and iNOS gene expression with different time-courses and distributions, and that iNOS mRNA was more frequently co-localized with CRF-producing parvocellular neurons in the PVN. Thus, NO produced by iNOS and nNOS may play an important role in the neuroendocrine response to an immune challenge. Distinct differences in the distribution and time-course changes of iNOS and nNOS suggest different roles for the hypothalamic-pituitary-adrenal axis and/or neurohypophyseal system.
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PMID:Distinct distribution and time-course changes in neuronal nitric oxide synthase and inducible NOS in the paraventricular nucleus following lipopolysaccharide injection. 1006 18