[Distribution of RNA during neuronal migration in developing normal and dysplastic brains in man. Acridine orange...

Acridine orange, a fluorochrome stain of nucleic acids, was used to study neuronal maturation in human brains during development. The central nervous system in 15 normal fetuses and neonates of 16 to 44 weeks gestational age were examined, as well as 24 dysplastic brains exhibiting abnormal cellular migrations. The increase in cytoplasmic RNA of neurons coincides with the onset of neurotransmitter synthesis, temporally synchronized to begin after migration in the cerebral hemispheres but before migration of the external granular layer of the cerebellum. The presence or absence of orange fluorescence in heterotopic nerve cells serves as a marker of the state of maturity by indicating whether the cell was still migrating at the time of death or had already arrived at its definitive site in the brain, whether normal or abnormal. Furthermore, the type of neurotransmitter produced by a given neuron influences ribosomal concentration and hence the intensity of orange RNA fluorescence. Neurons that secrete peptides, acetylcholine, or monoamines show stronger fluorescence than do those synthesizing simple amino acids as transmitters. Transitory transmitters of developing brain may account for stronger fluorescence in certain neurons of the fetus than in the adult, an example being the granule cells of the cerebellar cortex. Acridine orange is a useful supplementary tool in pediatric neuropathology.