The influence of chronic moderate ethanol administration on NADPH-diaphorase (nitric oxide synthase) activity in rat brain.
Nitric oxide synthase (NOS), the enzyme with reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase activity, generates nitric oxide (NO) which is an important bioregulatory molecule in the nervous, immune, and cardiovascular systems. NOS is linked to non-adrenergic non-cholinergic (NANC) neuronal pathways and modulation of the N-methyl-D-aspartate receptors, yet its modification by ethanol has been little explored. A possible modification by chronic ethanol administration of activity and/or localization of NADPH-diaphorase (NO-synthase) in rat brain may thus provide the pathogenic basis of alcohol-induced brain injury. When female Wistar rats were treated chronically with ethanol for 50 days, the NADPH-diaphorase staining of granular neurons and neurons located in the molecular layer of the cerebral cortex was significantly reduced. Chronic ethanol consumption led to a significant reduction in NADPH-diaphorase staining in the superficial layers of the superior colliculus. The number of NADPH-diaphorase-positive neurons was significantly reduced (P < 0.001) in the stratum zonale and stratum griseum superficiale (by 42.3-65.6% of control values). This could alter synaptic processes in the highly organized structures involved in oculomotor and somatic motor coordination and thus contribute to the motor disturbances which are associated with alcohol abuse.
First Institute of Medical Chemistry and Biochemistry, First Faculty of Medicine, Charles University, Prague, Czech Republic.
T
T
Zima
R
R
Druga
S
S
Stípek
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase