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Whole brain spheroid cultures as a model to study the development of nitric oxide synthase-guanylate cyclase signal transduction.
- Source :
-
Brain research. Developmental brain research [Brain Res Dev Brain Res] 2000 Dec 29; Vol. 125 (1-2), pp. 99-115. - Publication Year :
- 2000
-
Abstract
- Whole brain spheroids provide a suitable model to study neurodevelopment. In the literature a role for the nitric oxide (NO)-cyclic guanosine 3',5'-monophosphate (cGMP) signalling pathway during development has frequently been suggested. In this study we investigated whether functional cGMP pathways were present in differentiated spheroids. In 3-week-old spheroids soluble guanylate cyclase was stimulated with N-methyl D-aspartic acid or sodium nitroprusside (NO donor). The results showed that the NO synthase-cGMP pathway is present in the culture system. Soluble guanylate cyclase-dependent cGMP formation was found in NO synthase containing neurons, in neurons of the GABAergic, glutamatergic and cholinergic system, and in astroglia and oligodendroglia. Activation of particulate guanylate cyclase by atrial natriuretic peptide also triggered an increase in cGMP production. Particulate guanylate cyclase was found in astroglia and in microglia as well as in glutamic acid decarboxylase and calbindin containing structures and neuronal NO synthase containing neurons. Chronic inhibition of NO synthase during culture development had no effect on soluble or particulate guanylate cyclase functioning. Similarly, inhibition of soluble guanylate cyclase during culture development did not have any effect on NO synthase and particulate guanylate cyclase functioning. It is concluded that NO synthase and both soluble and particulate guanylate cyclase are present in whole brain spheroid cultures and that their activity can be influenced by several stimuli. The spheroid culture system constitutes a suitable model to study the NO-cGMP pathway during brain development in mammals.
- Subjects :
- 1-Methyl-3-isobutylxanthine pharmacology
Animals
Astrocytes cytology
Atrial Natriuretic Factor pharmacology
Brain enzymology
Brain growth & development
Cell Culture Techniques methods
Cells, Cultured
Cyclic GMP metabolism
Enzyme Inhibitors pharmacology
Excitatory Amino Acid Agonists pharmacology
Female
Guanylate Cyclase analysis
N-Methylaspartate pharmacology
NG-Nitroarginine Methyl Ester pharmacology
Neurons cytology
Nitric Oxide metabolism
Nitric Oxide Synthase analysis
Nitric Oxide Synthase Type I
Nitroprusside pharmacology
Oxadiazoles pharmacology
Phosphodiesterase Inhibitors pharmacology
Pregnancy
Quinoxalines pharmacology
Rats
Rats, Inbred Lew
Signal Transduction drug effects
Vasodilator Agents pharmacology
Astrocytes enzymology
Guanylate Cyclase metabolism
Neurons enzymology
Nitric Oxide Synthase metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0165-3806
- Volume :
- 125
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Brain research. Developmental brain research
- Publication Type :
- Academic Journal
- Accession number :
- 11154766
- Full Text :
- https://doi.org/10.1016/s0165-3806(00)00128-0