Romano Adele, Gallelli Cristina Anna, Koczwara Justyna Barbara, Braegger Fiona E, Vitalone Annabella, Falchi Mario, Micioni Di Bonaventura Maria Vittoria, Cifani Carlo, Cassano Tommaso, Lutz Thomas A, Gaetani Silvana
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
Institute of Veterinary Physiology, Vetsuisse Faculty University of Zurich (UZH), 8057, Zurich, Switzerland.
Pharmacol Res. 2017 Aug;122:20-34. doi: 10.1016/j.phrs.2017.05.017. Epub 2017 May 20.
The satiety-promoting action of oleoylethanolamide (OEA) has been associated to the indirect activation of selected brain areas, such as the nucleus of the solitary tract (NST) in the brainstem and the tuberomammillary (TMN) and paraventricular (PVN) nuclei in the hypothalamus, where noradrenergic, histaminergic and oxytocinergic neurons play a necessary role. Visceral ascending fibers were hypothesized to mediate such effects. However, our previous findings demonstrated that the hypophagic action of peripherally administered OEA does not require intact vagal afferents and is associated to a strong activation of the area postrema (AP). Therefore, we hypothesized that OEA may exert its central effects through the direct activation of this circumventricular organ. To test this hypothesis, we subjected rats to the surgical ablation of the AP (APX rats) and evaluated the effects of OEA (10mgkg i.p.) on food intake, Fos expression, hypothalamic oxytocin (OXY) immunoreactivity and on the expression of dopamine beta hydroxylase (DBH) in the brainstem and hypothalamus. We found that the AP lesion completely prevented OEA's behavioral and neurochemical effects in the brainstem and the hypothalamus. Moreover OEA increased DBH expression in AP and NST neurons of SHAM rats while the effect in the NST was absent in APX rats, thus suggesting the possible involvement of noradrenergic AP neurons. These results support the hypothesis of a necessary role of the AP in mediating OEA's central effects that sustain its pro-satiety action.
油酰乙醇胺（OEA）促进饱腹感的作用与特定脑区的间接激活有关，如脑干中的孤束核（NST）以及下丘脑的结节乳头体（TMN）和室旁核（PVN），其中去甲肾上腺素能、组胺能和催产素能神经元发挥着必要作用。内脏传入纤维被认为介导了这些效应。然而，我们之前的研究结果表明，外周给予OEA的促食欲作用并不需要完整的迷走神经传入，且与最后区（AP）的强烈激活有关。因此，我们推测OEA可能通过直接激活这个脑室周器官来发挥其中枢效应。为了验证这一假设，我们对大鼠进行了AP手术切除（APX大鼠），并评估了OEA（10mg/kg腹腔注射）对食物摄入、Fos表达、下丘脑催产素（OXY）免疫反应性以及脑干和下丘脑中多巴胺β羟化酶（DBH）表达的影响。我们发现，AP损伤完全阻断了OEA在脑干和下丘脑中的行为和神经化学效应。此外，OEA增加了假手术大鼠AP和NST神经元中DBH的表达，而在APX大鼠的NST中则没有这种效应，这表明去甲肾上腺素能AP神经元可能参与其中。这些结果支持了AP在介导OEA维持其促饱腹感作用的中枢效应中起必要作用的假设。
