Abstract
The carotid body is a highly specialized chemoreceptive structure for the detection of and reaction to hypoxia, through induction of an increase in hypoxia inducible factor. As tissue hypoxia increases with aging and can have dramatic effects in respiratory depression induced by drug addiction, we investigated the carotid body in young and old healthy subjects in comparison with drug-addicted subjects, including the expression of the neurotransmitter galanin. Galanin expression was recently reported for neuronal-like cells of the human carotid body, and it is implicated in several functions in neurons. In particular, this includes the regulation of differentiation of neural stem cells, and participation in the development and plasticity of the nervous system. Using immunohistochemistry detection, we demonstrate that galanin expression in the human carotid body in healthy older subjects and drug-addicted subjects is significantly reduced in comparison with healthy young subjects. This demonstrates not only the effects of normal aging and senescence, but also in the drug-addicted subjects, this appears to be due to a disorganization of the chemo-sensory region. With both aging and drug addiction, this results in a physiological reduction in neuronal-like cells, coupled with interlobular and intralobular increases in connective tissue fibers. Consequently, in both aging and drug addiction, this reduction of neuronal-like cells and the regeneration suggest that the carotid body is losing its sensory capabilities, with the transmission of chemoreceptive signals dramatically and vitally reduced. The level of galanin expression would thus provide a signal for neurogenesis in young subjects, and for neurodegeneration in older and drug-addicted subjects.
Highlights
In humans, the pleiotropic 30-amino-acid neuropeptide galanin is widely distributed in the central nervous system, where it is biologically active and participates in the modulation of several ascending neurotransmitter systems, including cholinergic, noradrenergic, and serotoninergic pathways (Tatemoto et al, 1983; Crawley et al, 2002)
In the young healthy subjects, positive galanin labeling was restricted to the sensory areas at the level of the neuronal-like cells, while in the older healthy subjects, the labeling was decreased in this area; there was a further dramatic reduction in galanin expression in the tissues from the drug-addicted subjects (Figure 3)
DISCUSSION increases in connective tissue fibers are not exclusive to the aging process, its occurrence in this young population of drug-addicted subjects suggests activation of an early aging mechanism in the carotid body that would be due to the hypoxia effects of drug addiction (Porzionato et al, 2005; Zara et al, 2013)
Summary
The pleiotropic 30-amino-acid neuropeptide galanin is widely distributed in the central nervous system, where it is biologically active and participates in the modulation of several ascending neurotransmitter systems, including cholinergic, noradrenergic, and serotoninergic pathways (Tatemoto et al, 1983; Crawley et al, 2002). Three galanin receptors have been identified (GalR1-3), and these signal through G-protein-coupled mechanisms in tissue-specific and cell-specific manners, to modulate a wide array of homeostatic and pathological processes (Counts et al, 2003). Galanin administration results in up-regulation of genes involved in pro-survival/proneuronal signaling pathways, and increases the number of neurons arising from differentiation of olfactory sensory neuron progenitors (Cordeo-Llana et al, 2014). Treatment of wild-type and GAL knock-out neural stem cells with galanin and the. Galanin regulates differentiating neural stem cells, and in this way it participates in the development and plasticity of the nervous system
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