Lavdas, Alexandros A.; (1997) The role of monoamines in the development of rat cortical neuronal types: An in vitro study. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

The monoamines serotonin (5-HT), noradrenaline (NE) and dopamine (DA), present in the developing brain long before they assume their neurotransmitter functions, are regarded as strong candidates for a role in the maturation of the cerebral cortex. Acetylcholine, although it appears in the cortex at more advanced developmental stages, has also been considered as a candidate. This study sought to investigate the effects of these neurotransmitters on the generation and differentiation of cortical cell types. Slice cultures, prepared from the cortices of embryonic day (E) 14, 16 and 19 rat embryos, were kept in defined medium or in defined medium plus 5-HT for 7 days. Embryonic day 16 cortices were also exposed to DA, NA or ACh for the same period. At the end of this period, the proportions of the neuronal (glutamate-, GABA-, calbindin-, calretinin- labelled), glial (GFAP) and neuroepithelial (nestin) cell types were estimated for all conditions. It was found that in E16 cultures, application of 5-HT, but not of DA, NA or ACh, significantly increased the proportion of glutamate containing neurons in a dose-dependent manner without affecting the proportions of any other cell types. A similar effect was observed in co-cultures of E16 cortex with slices through the midbrain of E19 embryos containing the raphe nuclei. The total amount of cortical glutamate, as measured with high pressure liquid chromatography, was also increased in these co-cultures. To investigate whether the effect of 5-HT was the result of changes in cell proliferation, cortical slices were exposed to bromodeoxyuridine (BrdU) every day of the culture period. Cell counts showed that the proportion of BrdU labelled cells was similar in the 5-HT treated and control slices. These results indicate that 5-HT promotes the differentiation of cortical glutamate containing neurons without affecting neuroepithelial cell proliferation.

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