Rowe, Sally Joy; (1991) The role of monoamines in the development of the amphibian embryonic nervous system. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This study investigated the role of monoamines in the phenotypic differentiation of CNS neurones in the Xenopus laevis embryo. Treatment of neurulating embryos with a-adrenergic receptor antagonists inhibited subsequent neuronal differentiation. Results were assessed quantitatively, using a tissue culture method, and qualitatively, by histological methods. Antagonists of other types of neurotransmitter receptor did not inhibit neuronal differentiation. β-Adrenergic receptor blockade was effective throughout neurulation but ineffective after neural tube closure. Inhibition of neuronal differentiation by β-adrenergic receptor blockers was prevented by β-adrenergic receptor agonists and monoamines. The use of inhibitors of catecholamine biosynthetic enzymes established that noradrenaline prevented the inhibition of neuronal differentiation. The effects of blocking the sodium pump during mid-neural fold stages on neuronal differentiation were also overcome by monoamines. Again, the inclusion of enzyme inhibitors showed that noradrenaline was responsible for reversing the effects of strophanthidin. The effect on normal development of inhibiting catecholamine biosynthesis was examined. Preventing the conversion of dopamine to noradrenaline during neurulation significantly inhibited the subsequent differentiation of neurones and confirmed that noradrenaline played a role in the control of neuronal differentiation. Preliminary investigations were conducted into the mechanisms by which noradrenaline could affect neuronal differentiation, including the role of second messengers produced as a consequence of receptor activation. The effect of manipulating the ionic environment during a-adrenergic receptor blockade was tested and provided further evidence that a-adrenergic receptor activation and switching on of the sodium pump exerted their effects on neuronal differentiation by different pathways. It was concluded that the activation of an atypical a-adrenergic receptor by an endogenous monoamine at neural plate stages is necessary for the subsequent differentiation of neurones. It is unlikely that a monoamine switches on the sodium pump directly. The results described here suggest that the two mechanisms could act synergistically.

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