Satb2-Independent Acquisition of the Cholinergic Sudomotor Phenotype in Rodents

Abstract

Expression of Satb2 (Special AT-rich sequence-binding protein-2) elicits expression of the vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) in cultured rat sympathetic neurons exposed to soluble differentiation factors. Here, we determined whether or not Satb2 plays a similar role in cholinergic differentiation in vivo, by comparing the postnatal profile of Satb2 expression in the rodent stellate ganglion to that of VAChT and ChAT. Throughout postnatal development, VAChT and ChAT were found to be co-expressed in a numerically stable subpopulation of rat stellate ganglion neurons. Nerve fibers innervating rat forepaw sweat glands on P1 were VAChT immunoreactive, while ChAT was detectable at this target only after P5. The postnatal abundance of VAChT transcripts in the stellate ganglion was at maximum already on P1, whereas ChAT mRNA levels increased from low levels on P1 to reach maximum levels between P5 and P21. Satb2 mRNA was detected in cholinergic neurons in the stellate ganglion beginning with P8, thus coincident with the onset of unequivocal detection of ChAT immunoreactivity in forepaw sweat gland endings. Satb2 knockout mice exhibited no change in the P1 cholinergic VAChT/ChAT co-phenotype in stellate ganglion neurons. Thus, cholinergic phenotype maturation involves first, early target (sweat-gland)-independent expression and trafficking of VAChT, and later, potentially target- and Satb2-dependent elevation of ChAT mRNA and protein transport into sweat gland endings. In rat sudomotor neurons that, unlike mouse sudomotor neurons, co-express calcitonin gene-related peptide (CGRP), Satb2 may also be related to the establishment of species-specific neuropeptide co-phenotypes during postnatal development.

Dramatically Amplified Thoracic Sympathetic Postganglionic Excitability and Integrative Capacity Revealed with Whole-Cell Patch-Clamp Recordings

“…We found that TH + neurons comprised >97% of the population and no ganglion contained >6% presumptive cholinergic neurons. This agrees with prior findings in rodent thoracic ganglia which found few cholinergic neurons (Schäfer et al, 1998; Jobling and Gibbins, 1999; Masliukov and Timmermans, 2004; Schütz et al, 2015; see also Furlan et al, 2016). This indicates that cholinergic neurons in thoracic ganglia are rare.…”

Cholinergic- rather than adrenergic-induced sweating play a role in developing and developed rat eccrine sweat glands

“…Therefore, species, forepaws or hind paws, and different markers might account for the discrepancies of the initially detected time point of sweat gland innervations. Nonetheless, cholinergic fibers appeared slightly later than adrenergic fibers in the developing rat/mouse footpads, and the co-expression of adrenergic and cholinergic fibers in adult rat/mouse eccrine sweat glands were consistent in most studies [4,16,19,[22][23][24][25].…”

“…Another study by Schütz et al showed that an adrenergic-specific TH was detectable at P1 and a cholinergic-specific vesicular acetylcholine transporter (VAChT) was visible at P3 in eccrine sweat glands of mouse forepaws [22]. Further studies showed that cholinergic fiber markers VAChT, choline acetyltransferase (ChAT) and calcitonin gene-related peptide (CGRP) appeared at different time points [23]. Discrete VAChT-immunoreactivities were present at P1, sparse ChAT immunoreactivity was detected at P8, and unequivocally detectable CGRP appeared at P14 in forepaw sweat glands of Wistar rats [23].…”

“…Further studies showed that cholinergic fiber markers VAChT, choline acetyltransferase (ChAT) and calcitonin gene-related peptide (CGRP) appeared at different time points [23]. Discrete VAChT-immunoreactivities were present at P1, sparse ChAT immunoreactivity was detected at P8, and unequivocally detectable CGRP appeared at P14 in forepaw sweat glands of Wistar rats [23]. A study by Guidry et al showed that TH-positive fibers were readily detected surrounding the developing sweat at P5, and weak choline transporter (CHT) expression appeared in the fibers innervating sweat gland anlagen at P7 in mouse and P10 in rat gland anlages of hind footpads [24].…”

Epidemiology of dermatological diseases - aging, metabolic diseases and beyond

“…Recording skin sympathetic nerve activity has revealed that a large fraction of the sympathetic activity during heat stress is essentially sudomotor in nature through acetylcholine release that binds to muscarinic receptors. Other neural systems may be involved (e.g., α-or β-adrenergic, vasoactive intestinal polypeptide, calcitonin gene-related peptide) [12][13][14]. The human skin and its sebaceous glands express a plethora of neuropeptidergic receptors -e.g., corticotropin-releasing hormone, transient receptor potential vanilloid-1, melanocortins, β-endorphin, vasoactive intestinal polypeptide, neuropeptide Y, substance P, and calcitonin gene-related peptide which may become dysfunctional or with altered expression levels [15,16].…”