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The satiety signal oleoylethanolamide stimulates oxytocin neurosecretion from rat hypothalamic neurons

By August 22, 2013No Comments

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The satiety signal oleoylethanolamide stimulates oxytocin neurosecretion from rat hypothalamic neurons

  • a Department of Physiology and Pharmacology, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
  • b Department of Clinical and Experimental Medicine, University of Foggia, Viale Luigi Pinto, 1 c/o OO.RR., 71100 Foggia, Italy
  • c Institute of Cell Biology and Neurobiology, National Research Council of Italy (C.N.R.), Via del Fosso di Fiorano 64, 00143 Rome, Italy

Highlights

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The administration of OEA increases oxytocin expression in neurons of the PVN.

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Causes oxytocin accumulation at the nerve endings in the neurohypophysis.

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Stimulates oxytocin neurosecretion at the somatodendritic level in the PVN.

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OEA may represent a novel target for modulating the oxytocinergic system.

 

Abstract

The anandamide monounsaturated analogue oleoylethanolamide (OEA) acts as satiety signal released from enterocytes upon the ingestion of dietary fats to prolong the interval to the next meal. This effect, which requires intact vagal fibers and intestinal PPAR-alpha receptors, is coupled to the increase of c-fos and oxytocin mRNA expression in neurons of the paraventricular nucleus (PVN) and is prevented by the intracerebroventricular administration of a selective oxytocin antagonist, thus suggesting a necessary role of oxytocinergic neurotransmission in the pro-satiety effect of OEA. By brain microdialysis and immunohistochemistry, in this study we demonstrate that OEA treatment can stimulate oxytocin neurosecretion from the PVN and enhance oxytocin expression at both axonal and somatodendritic levels of hypothalamic neurons. Such effects, which are maximum 2 h after OEA administration, support the hypothesis that the satiety-inducing action of OEA is mediated by the activation of oxytocin hypothalamic neurons.

Figures and tables from this article:

Full-size image (61 K)
Fig. 1. OEA increases oxytocin immunoreactivity in the PVN. (A) Representative images of oxytocin immunostaining of brain slices obtained from rats treated with vehicle or OEA (10 mg kg−1, i.p.) and sacrificed at different time points (1, 2 and 4 h). All the wide panels show images taken at the magnification of 2×; all the squared smaller panels show images taken at the magnification of 10× corresponding to the areas highlighted with red dotted squares on the wide panels. Scale bars = 500 μm. (B) Results obtained by the semiquantitative analysis of the optical densities of immunolabeled PVN measured in rats treated with OEA (10 mg kg−1, i.p., black histograms) or vehicle (saline, PEG, Tween 80 5/5/90, 2 ml kg−1, white histograms) and sacrificed at different time points (1, 2 and 4 h), expressed in arbitrary units as mean ± SEM. *p < 0.05 vs vehicle (Tukey’s test, n = 7).
Full-size image (71 K)
Fig. 2. OEA stimulates the somatodendritic release of oxytocin from PVN neurons. (A) Representative images of rat pituitary glands showing pituicyte nuclei staining (blue), oxytocin immunofluorescence (green) and merge of both taken at the magnification of 2×. The red dotted square area is shown separately at a higher magnification (40×) in the right panels. Scale bar = 250 μm. (B) Results obtained by the semiquantitative analysis of the optical densities of oxytocin immunolabeled pituitary glands collected from rats treated with OEA (10 mg kg−1, i.p., black histograms) or vehicle (saline, PEG, Tween 89 5/5/90, 2 ml kg−1, white histograms) and measured in the three different portions of the gland (adeno-hypophysis, intermediate-hypophysis, neuro-hypophisis). Data are expressed in arbitrary units as mean ± SEM. ***p < 0.01 vs vehicle (Tukey’s test, n = 6). (C) Diagram of a coronal section of the rat brain showing the localization of the microdialysis probe. The right panel shows at higher magnification the map of hits for probe placement. (D) Time-course effects of OEA (10 mg kg−1, red line and red square symbols) on the extracellular levels of oxytocin measured in the PVN of freely moving rats through microdialysis and EIA analysis of dialysates. *p < 0.05 vs respective control (circled black symbols and black line, Tukey’s test, n = 7). (For interpretation of the references to color in the text, the reader is referred to the web version of the article.)
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