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)

Narcolepsy is characterized by excessive sleepiness and episodes of cataplexy brought on by emotional excitation. Cataplexy and sleep paralysis have been hypothesized to be produced by the triggering during waking of brain stem cholinergic mechanisms normally acting to induce atonia in REM sleep. We hypothesized that narcoleptics have an abnormal number of LDT and/or PPN cholinergic neurons. A comparison was made of cholinergic cell numbers in the brain stems of normal and narcoleptic canines. Cholinergic neurons were identified by NADPH-diaphorase histochemistry. We found increased numbers of cholinergic neurons at the R6-R7 level of the LDT and PPN in narcoleptic canines. This abnormality can explain alterations in cholinergic receptor number, acetylcholine release, and the occurrence of cataplexy and sleep paralysis that characterize narcolepsy.
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PMID:Altered distribution of cholinergic cells in the narcoleptic dog. 757 39

Canine narcolepsy is a unique experimental model of a human sleep disorder characterized by excessive daytime sleepiness and cataplexy. There is a consensus recognition of an imbalance between cholinergic and catecholaminergic systems in narcolepsy although the underlying mechanisms remain poorly understood. Possible substrates could be an abnormal organization, numbers and/or ratio of cholinergic to catecholaminergic cells in the brain of narcoleptic dogs. Therefore, we sought to characterize the corresponding neuronal populations in normal and narcoleptic dogs (Doberman Pinscher) by using choline acetyltransferase (ChAT), nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase, tyrosine hydroxylase (TH), and dopamine beta-hydroxylase (DBH). Cholinergic cell groups were found in an area extending from the central to the gigantocellular tegmental field and the periventricular gray corresponding to the pedunculopontine tegmental nucleus (PPT), the laterodorsal tegmental nucleus (LDT), and the parabrachial nucleus. An almost perfect co-localization of ChAT and NADPH-diaphorase was also observed. Catecholaminergic cell groups detected included the ventral tegmental area, the substantia nigra, and the locus coeruleus nucleus (LC). The anatomical distribution of catecholaminergic neurons was unusual in the dog in two important aspects: i) TH- and/or DBH-immunoreactive neurons of the LC were found almost exclusively in the reticular formation and not within the periventricular gray, ii) very few, if any TH-positive neurons were found in the central gray and dorsal raphe. Quantitative analysis did not reveal any significant differences in the organization and the number of cells identified in the LDT, PPT, and LC of normal and narcoleptic dogs. Moreover, the cholinergic to catecholaminergic ratio was found identical in the two groups. In conclusion, the present results do not support the hypothesis that the neurochemical imbalance in narcolepsy could result from abnormal organization, numbers, or ratio of the corresponding neuronal populations.
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PMID:Mesopontine organization of cholinergic and catecholaminergic cell groups in the normal and narcoleptic dog. 905 Jul 84