Introduction: an overview

Primary functions of norepinephrine during brain development

Catecholamines are essential to normal neuronal development and thus can be detected from early ontogenesis onwards. The cellular environment influences which type of neurotransmitter (e.g. adrenergic or cholinergic) a neuron will produce. Glucocorticoids, for example, can affect the differentiation of neural crest cells in an adrenergic direction, at least in vitro. Norepinephrine (NE) is found in early cortical structures, and is probably required for appropriate migration and apoptosis of neurons, as well as for laminar formation and glial development. The crucial importance of NE in development has been shown by Thomas et al. These researchers produced mice completely lacking NE production due to the absence of the gene for dopamine-β-hydroxylase, and showed that this state led to death in utero from day 11 of gestation onwards. A small percentage of homozygous pups born to heterozygous mothers did survive, probably due to transplacental passage of maternal NE. In other cases, fetuses could only be rescued by adding an NE precursor that did not require conversion by dopamine-β-hydroxylase to the maternal drinking water during pregnancy, indicating that the presence of NE during development is essential for survival.

Primary functions of norepinephrine in the mature CNS

Norepinephrine neurons in the central nervous system (CNS) originate mainly from two cell groups: the lateral tegmentum area sends fibers through the ventral ascending noradrenergic bundle innervating the hypothalamic, basal telencephalic, and preoptic areas.