Developmental Regulation of Neurotransmitters in Sympathetic Neurons

Abstract

Publisher Summary Sweat glands are innervated exclusively by cholinergic sympathetic neurons. Several studies summarized in this chapter indicate that the cholinergic differentiation factor produced by sweat glands is a novel member of the neuropoietic cytokine family. The changes in neurotransmitter properties that occur during normal development of the sweat gland innervation can be induced in cultured sympathetic neurons by members of the neuropoietic cytokine family, including leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1) but not by other cytokines and growth factors. Further, monoclonal antibodies that block activation of LIFR β , one of the receptor subunits utilized by members of the neuropoietic cytokine family, block the induction of cholinergic function in sweat glandhympathetic neuron cocultures. Although, the studies on adult mice deficient in LIF, CNTF, or LIF and CNTF have revealed that the sweat gland innervation possessed cholinergic and peptidergic properties. Similarly, the induction of cholinergic and peptidergic properties in sympathetic neurons cocultured with sweat gland cells is not prevented by the presence of antibodies that block CT-1 function. Thus, the known members of the neuropoietic cytokine family do not appear to account for the cholinergic induction by sweat glands. In addition, culture studies suggest that the catecholamines produced by the early innervation are important in its regulation. Recently the periosteum or connective tissue covering of the bone has been identified a new cholinergic sympathetic target. Like the developing sweat gland innervation, periosteal innervation initially expresses noradrenergic properties that are suppressed as cholinergic and peptidergic ones appear, and this change is regulated by interactions with the target. In contrast to the developing sweat gland innervation, a significant proportion of the sympathetic axons that reach the sternum have already expressed immunoreactivity for the vesicular acetylcholine transporter (VAChT) and vasoactive intestinal peptide (VIP) in addition to catecholaminergic properties.