The Canine Sympathetic Neuropeptide Galanin: A Neurotransmitter in Pancreas, A Neuromodulator in Liver

Taborsky, Gerald J.; Dunning, Beth E.; Havel, Peter J.; Åhrén, Bo; Kowalyk, Stephan; Boyle, M. R.; Verchere, C. Bruce; Baskin, Denis G.; Mundinger, Thomas O.

doi:10.1055/s-2007-978752

Cited by 17 publications

(16 citation statements)

References 15 publications

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“…Other data show galanin co-localization in sympathetic nerve fibers, but this was performed in dog liver. Most likely, galanin in these nerves acts as a neuromodulator and has a potential role in hepatic glucose release [25,26].…”

Section: Discussionmentioning

confidence: 99%

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Thoene

Godlewski

Rytel

et al. 2018

Folia Histochem Cytobiol.

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Introduction. Bisphenol A (BPA) is used in the chemical industry for manufacturing plastics which are used as food packaging. Data indicate that BPA is released from such products and is widely present in the environment and the human body. So far, the EFSA and the US FDA have determined "safe" BPA oral exposure levels, and a large amount of data indicates that BPA is harmful even at low-doses. Our previously performed analyses concerning BPA exposure demonstrated the impact of this substance on parasympathetic and peptidergic nerve fibers present within the liver. Therefore, this study concerns BPA exposure and sympathetic intrahepatic innervation in reference to several neuropeptides which modulate neuronal responses: cocaine and amphetamine regulated transcript (CART), galanin (GAL), calcitonin gene-regulated peptide (CGRP) and substance P (SP). Materials and methods. Fifteen young swine at 8 weeks of age were used as experimental models of the juvenile human liver. The pigs were divided into 3 groups and received capsules orally with bisphenol at a dose of 0.05 mg/kg b.w./day; a dose of 0.5 mg/kg b.w./day and placebo capsules as a control. After 28 days of oral BPA intake, the animals were euthanized, perfused with 4% paraformaldehyde (PFA), and livers were collected and fixed in PFA. The cryostat sections were subjected to a routine double-labeling immunofluorescence technique. The primary antibodies were directed against dopamine beta hydroxylase (DbH), which is a marker for sympathetic nerves, and one of the investigated neuropeptides: CART, GAL, CGRP and SP, which co-localized the investigated nerves. Immunoreactive nerves were counted in the liver and the percentage presence of each neuronal combination in particular samples of each experimental group were determined and analyzed statistically. Results. The BPA oral intake at low and ten times higher dosage caused an increase of the number of sympathetic nerve fibers within the porcine liver by 48.6% and 63.7%, respectively. Moreover, BPA exposure caused an increased presence of sympathetic nerve fibers in these two experimental groups, which were co-localized with CART and GAL up to 65.9%/173.2% and 147.4%/126.3%, respectively. At the lower BPA doses of 50 μg/kg b.w./day, the percentages of SP+/DbH+ and CGRP+/DbH+ nerve fibers were similar to the control. 114Michael Thoene et al. However at a ten times higher dose, BPA caused an increased number of SP+/ DbH+ and CGRP+/ DbH+ nerve fibers in the liver, up to 46.4% and 73.5% respectively. Conclusions. BPA caused an increase in the number of sympathetic nerve fibers as well as sympathetic nerve fibers which co-localized with neuropeptides in the porcine liver. The increase in CART and GAL were exceptionally high even at low BPA doses. BPA food contamination may dysregulate liver sympathetic innervation, and thereby may change the oxygenated blood supply, alter metabolism and disrupt the activity of hepatic parenchymal cells.

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Section: Discussionmentioning

confidence: 99%

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Thoene

Godlewski

Rytel

et al. 2018

Folia Histochem Cytobiol.

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“…neurotransmitter, has no effects on its own when infused into the portal vein, but it does potentiate the action of norepinephrine to stimulate hepatic glucose production [249].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

The role of the autonomic nervous liver innervation in the control of energy metabolism

Fleur²,

Fliers³

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

172

192

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Despite a longstanding research interest ever since the early work by Claude Bernard, the functional significance of autonomic liver innervation, either sympathetic or parasympathetic, is still ill defined. This scarcity of information not only holds for the brain control of hepatic metabolism, but also for the metabolic sensing function of the liver and the way in which this metabolic information from the liver affects the brain. Clinical information from the bedside suggests that successful human liver transplantation (implying a complete autonomic liver denervation) causes no life threatening metabolic derangements, at least in the absence of severe metabolic challenges such as hypoglycemia. However, from the benchside, data are accumulating that interference with the neuronal brain-liver connection does cause pronounced changes in liver metabolism. This review provides an extensive overview on how metabolic information is sensed by the liver, and how this information is processed via neuronal pathways to the brain. With this information the brain controls liver metabolism and that of other organs and tissues. We will pay special attention to the hypothalamic pathways involved in these liver-brain-liver circuits. At this stage, we still do not know the final destination and processing of the metabolic information that is transferred from the liver to the brain. On the other hand, in recent years, there has been a considerable increase in the understanding which brain areas are involved in the control of liver metabolism via its autonomic innervation. However, in view of the ever rising prevalence of type 2 diabetes, this potentially highly relevant knowledge is still by far too limited. Thus the autonomic innervation of the liver and its role in the control of metabolism needs our continued and devoted attention.

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“…In comparison to the above five neuropeptidergic nerves, there is much less information about the distribution of other neuropeptidergic nerves, including glucagon‐ (Sasaki et al, 1984; Carlei et al, 1988; el Salhy et al, 1993), glucagon‐like peptide‐ (el Salhy et al, 1993), serotonin‐ (el Salhy et al, 1993; Carrier and Connat, 1995), neurotensin‐ (el Salhy et al, 1993), and galanin‐containing nerve (Mundinger et al, 1997; Akiyoshi et al, 1998; Taborsky et al, 1999). Furthermore, the distribution of these nerves is a controversial issue.…”

Section: Nerve Distribution In Liver Tissuementioning

confidence: 99%

Neural connections between the hypothalamus and the liver

2004

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After receiving information from afferent nerves, the hypothalamus sends signals to peripheral organs, including the liver, to keep homeostasis. There are two ways for the hypothalamus to signal to the peripheral organs: by stimulating the autonomic nerves and by releasing hormones from the pituitary gland. In order to reveal the involvement of the autonomic nervous system in liver function, we focus in this study on autonomic nerves and neuroendocrine connections between the hypothalamus and the liver. The hypothalamus consists of three major areas: lateral, medial, and periventricular. Each area has some nuclei. There are two important nuclei and one area in the hypothalamus that send out the neural autonomic information to the peripheral organs: the ventromedial hypothalamic nucleus (VMH) in the medial area, the lateral hypothalamic area (LHA), and the periventricular hypothalamic nucleus (PVN) in the periventricular area. VMH sends sympathetic signals to the liver via the celiac ganglia, the LHA sends parasympathetic signals to the liver via the vagal nerve, and the PVN integrates information from other areas of the hypothalamus and sends both autonomic signals to the liver. As for the afferent nerves, there are two pathways: a vagal afferent and a dorsal afferent nerve pathway. Vagal afferent nerves are thought to play a role as sensors in the peripheral organs and to send signals to the brain, including the hypothalamus, via nodosa ganglia of the vagal nerve. On the other hand, dorsal afferent nerves are primary sensory nerves that send signals to the brain via lower thoracic dorsal root ganglia. In the liver, many nerves contain classical neurotransmitters (noradrenaline and acetylcholine) and neuropeptides (substance P, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, glucagon, glucagon-like peptide, neurotensin, serotonin, and galanin). Their distribution in the liver is species-dependent. Some of these nerves are thought to be involved in the regulation of hepatic function as well as of hemodynamics. In addition to direct neural connections, the hypothalamus can affect metabolic functions by neuroendocrine connections: the hypothalamus-pancreas axis, the hypothalamus-adrenal axis, and the hypothalamus-pituitary axis. In the hypothalamus-pancreas axis, autonomic nerves release glucagon and insulin, which directly enter the liver and affect liver metabolism. In the hypothalamus-adrenal axis, autonomic nerves release catecholamines such as adrenaline and noradrenaline from the adrenal medulla, which also affects liver metabolism. In the hypothalamuspituitary axis, release of glucocorticoids and thyroid hormones is stimulated by pituitary hormones. Both groups of hormones modulate hepatic metabolism. Taken together, the hypothalamus controls liver functions by neural and neuroendocrine connections.

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The Canine Sympathetic Neuropeptide Galanin: A Neurotransmitter in Pancreas, A Neuromodulator in Liver

Cited by 17 publications

References 15 publications

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

The role of the autonomic nervous liver innervation in the control of energy metabolism

Neural connections between the hypothalamus and the liver

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