Neurochemical differentiation of functionally distinct populations of autonomic neurons

Abstract

The coeliac ganglion of guinea pigs displays a unique topographical arrangement of neurochemically and functionally distinct populations of sympathetic neurons. The authors used multiple-labeling immunohistochemistry to investigate the neurochemical differentiation of these neurons during embryonic and fetal development. Sympathoadrenal precursors, located on either side of the abdominal aorta, were intensely immunoreactive for tyrosine hydroxylase (TH-IR), neurofilament, and the human natural killer 1 antibody at midembryonic stages (Carnegie stages 16-19). During late embryonic stages (stages 20-23), a single bilobed ganglion had formed. At this time, neuropeptide Y immunoreactivity (NPY-IR) was widely expressed in sympathetic neurons (with moderate TH-IR) and chromaffin cells (with intense TH-IR). The onset of somatostatin (Som-IR) expression followed that of NPY-IR and was restricted to sympathetic neurons. However, at late embryonic stages, most TH-IR neurons with Som-IR also expressed NPY-IR (a combination of peptides not found in the mature coeliac ganglion). Between late embryonic stages and the end of the early fetal period, there was a significant increase in the proportion of neurons in lateral regions that had both NPY-IR and TH-IR. At the same time, there was an increase in the proportion of neurons in medial regions that had both Som-IR and TH-IR. Neurons expressing both Som-IR and TH-IR were rarely observed in lateral regions of the coeliac ganglion. Thus, a clear topography within the coeliac ganglion is established during late embryonic and early fetal stages of development and reflects that found in the mature animal by the end of the early fetal period.

The cortistatin gene PSS2 rather than the somatostatin gene PSS1 is strongly expressed in developing avian autonomic neurons

“…However, our studies suggest that it will be essential to determine whether the SOM‐LIR in sensory neurons is due to somatostatin or cortistatin. Our data also raise the issue of whether the subpopulation of prevertebral sympathetic neurons observed in the celiac ganglion of adult guinea pigs that label with antibodies prepared against SOM‐14 are actually expressing somatostatin or cortistatin (Anderson et al,2001).…”

“…Neurons with somatostatin‐like immunoreactivity (SOM‐LIR) are also found in enteric, sympathetic, and parasympathetic ganglia of the mature autonomic nervous system. SOM‐LIR is expressed in cholinergic enteric neurons and a subset of neurons in parasympathetic ganglia; in the superior cervical ganglion, SOM‐LIR is expressed in a small subpopulation of neurons (Lundberg et al,1982; Wright and Luebke,1989), whereas more SOM‐LIR neurons are seen in trunk prevertebral ganglia (Hökfelt et al,1977; Anderson et al,2001). It has been assumed that SOM‐LIR is due to the presence of SOM‐14 or its N‐terminal extended SOM‐28; however, with the discovery of two genes that encode highly similar mature peptides, it is not clear whether the SOM‐LIR observed is actually due to transcription of the PSS1 or PSS2 gene.…”

Neuropeptide Y induces migration, proliferation, and tube formation of endothelial cells bimodally via Y1, Y2, and Y5 receptors

“…The presence of two maxima, one at very low NPY concentrations (pM) and one at very high concentrations (10 nM) not only indicates that NPY is one of the most potent angiogenic peptides known, but also that it can induce blood vessel formation over a wide range of concentrations. For instance, NPY-induced angiogenesis can occur in tissues that contain low NPY concentrations, such as the nonsympathetically innervated aorta or growing organs lacking a mature NPY system (29). Nevertheless, it can occur in tissues containing high NPY concentrations, such as the heart, mature vessels, or muscles during high sympathetic activity induced by stress, ischemia, or injury (11,18,30,31).…”

Relevance of the Neuropeptide Y System in the Biology of Cancer Progression

“…NPY-driven angiogenesis has been proposed to be bimodal at least in vitro (at low and high concentration, 10 -12 and 10 -8 M, respectively) and through oligomerization of Y1-, Y2-, and Y5-R. These data might explain the in vivo NPY-induced angiogenesis both in tissues that contain low NPY concentrations, such as the nonsympathetically innerved aorta or growing organs lacking a mature NPY system [46] and in tissues containing high NPY concentrations, such as the heart, mature vessels or muscles during high sympathetic activity induced by stress, ischemia, or injury [34,47]. Moreover, treatment with NPY and specific compounds, such as NPY 3-36 (Y2-R/Y3-R/Y5-R agonist), [Ala 31 , Aib 32 ]-NPY (Aib stands for -amino isobutyric acid; specific Y5-R agonist), [Ahx [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ]-NPY (specific Y2-R agonist) and specific Y2-R antagonist (BIIE0246TF) and Y5-R antagonist (CGP71683A) (see chemical structures in [111]), have demonstrated that: a) heterotrimers (Y1-R/Y2-R/Y5-R) are required for migration, b) heterodimers (Y1-R+Y2-R; Y1-R+Y5-R, or Y2-R+Y5-R) for proliferation and c) monomers (Y1-, Y2-, or Y5-R) for differentiation [11].…”