Gangliosides alter morphology and growth of astrocytes and increase the activity of choline acetyltransferase in cultures of dissociated septal cells.
Administration of gangliosides has been reported to stimulate regeneration of motoneurons and of central dopaminergic and cholinergic neurons. To shed light on the mechanism by which gangliosides mediate the effects on cholinergic neurons, we studied their actions on cultures of cells dissociated from the septal area of fetal rat brains. These cultures contain cholinergic neurons, which, in vivo, give rise to the cholinergic septo-hippocampal pathway. Gangliosides produced prominent changes in the morphological appearance of the cultures. In contrast to control cultures, which contained many process-bearing cells and a confluent layer of flat cells, there were no flat cells in cultures grown in the presence of gangliosides (0.2 to 0.8 mg/ml of medium). Using immunocytochemical visualization of the astrocytic marker glial fibrillary acid protein, it was shown that all astrocytes in cultures grown in the presence of gangliosides exhibited the morphology of process-bearing cells, whereas in control cultures astrocytes represented the majority of the flat cells. Furthermore, gangliosides attenuated astrocytic proliferation. The effects of gangliosides apparently were not mediated by cAMP, since they could be differentiated from actions of forskolin, an activator of adenylate cyclase. Astrocytic growth and morphology were affected by ganglioside mixtures of various sources and composition and also by the pure gangliosides GM1 and GD1a, whereas lipid and carbohydrate components of gangliosides were ineffective. In contrast to the prominent effects on astrocytes, gangliosides failed to significantly alter survival or fiber growth of cholinergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000166:cytology* / Q000201:enzymology
D004224:Diterpenes; D005732:Gangliosides; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; C021298:ganglioside, GD1a; D005576:Colforsin; D005677:G(M1) Ganglioside; D002795:Choline O-Acetyltransferase