Effects of catecholamine and serotonin in central nervous system in newborn mice with special reference to neural crest cells; presumptive evidence of neural crest origin.

Catecholamine and serotonin injected i.p. to new-born mice caused gliomas, ependymomas and choroid plexus papilloma together with multiple APUDomas within 48 hours after injection. We consider that an error in neural crest DNA may be caused through an adenylate-cyclic AMP system and Ca++ during replication and/or transcription. Multiple brain tumors caused by catecholamine and serotonin give the presumptive evidence that stem cells of neuroglia may be of neural crest origin.

Exposure of newborn mice to adenosine causes neural crest dysplasia and tumor formation.

In the first part of this paper, we show that intraperitoneal injection of adenosine into newborn mice causes multiple neural crest tumors, neural crest hyperplasia, and heterotopic melanin pigmentation. In the second part, we review published data to propose (1) that microtubule proteins, phosphorylated through the action of calmodulin-dependent kinase and cyclic adenosine monophosphate and the adenosine A2 receptor of neural crest cells, may participate in neurotransmission and (2) that at least some neural crest tumors may be associated with disorders of neurotransmission in embryonic neural crest cells.

Relationships between neural crest cells and serotonin in newborn mice.

The experimental newborn mice injected intraperitoneally with serotonin within 24 h after birth and survived up to 2-days showed multiple APUDomas, hyperplasia, heterotopic melanin pigmentation and the cell death of neural crest cells. Further, the degeneration occurred in the Auerbach, Meisner nerve plexus, autonomic ganglia. The flocculent densities were seen in the brain, and in the pulps and the periodontal membrane of teeth. It is thought that these phenomena may be associated with not only cyclic AMP but also calcium, and that neural crest cells may be autoreceptor.

Dysdifferentiation of neural crest cells by temperature in newborn mice.

Multiple neural crest tumors, hyperplasia, excessive cell proliferation, the cell death of neural crest cells and melanin pigmentation occurred in newborn mice injected intraperitoneally with heated deionized water. It is thought that these phenomena may not only be associated with the protein denaturation of the membrane structure in the neural crest cells, but also with temperature dependent changes of lipid-lipid and lipid-protein interactions, particularly changes of the mobility of proteins, and that may be a reflection of thermodynamic decrease in entropy that occurs during differentiation.

Effects of EDTA in newborn mice with special reference to neural crest cells.

Newborn mice were injected with measured doses of EDTA, resulting in the development of a complex of multiple neural crest tumors, hyperplasia, excessive cell proliferation, cell death of neural crest cells and heterotopic melanin pigmentation in the sites where the neural crest cells are present. The occurrence of multiple neural crest tumors as well as the mechanism of EDTA as a teratogen may be associated with cell membrane perturbation. Oncogenesis of neural crest tumors and cell death of neural crest cells from a single agent showed the complexity and variability of phenotypic expression. Neural crest cells may differentiate into many divergent cellular phenotypes derived from an initially undifferentiated stem cell population.

Relationships between neural crest cells and mast cells in newborn mice.

Histamine and EDTA injected to new born mice within 24 h after birth caused mastocytosis, cell death of neural crest cells and the appearance of mast cells in the specific sites where the neural crest cells were present. Mastocytes were composed of atypical cell such as round cells and spindle shaped cells in newborn mice treated with histamine and EDTA. The calcium perturbant in the histamine and EDTA may have caused these phenomena. Ca++ may be an essential conditional element in the differentiation to mast cells from neural crest cells.