Song Cai, Li Xuwen, Kang Zhijian, Kadotomi Yoshie
Department of Biomedical Sciences, AVC, University of Prince Edward Island, Charlottetown, PE, Canada.
Neuropsychopharmacology. 2007 Mar;32(3):736-44. doi: 10.1038/sj.npp.1301117. Epub 2006 Jun 14.
Previously, we have reported that interleukin-1 beta (IL-1) induces changes in dopaminergic (DA) and serotonergic systems in the core of the [corrected] nucleus accumbens (NAc). We have also demonstrated that n-3 fatty acid ethyl-eicosapentaenoate (EPA) can significantly reduce stress and anxiety-like behaviors, corticosterone concentrations [corrected] and peripheral inflammatory response induced by IL-1 administration. Compared to the core, the shell is involved more in emotion, stress and psychiatric diseases. However, the relationship between inflammation and the functions of DA system in the shell has not been studied. Since phospholipase (PL) A2 is a key enzyme in the [corrected] arachidonic acid-eicosanoids-prostaglandin [corrected] (PG)E2 pathway, and the change in NAc DA [corrected] system has been associated with glucocorticoid stimulation; [corrected] therefore, the hypotheses of this study are (1) that IL-1 induced changes in DA neurotransmission in the shell may be through PLA2-PGE2-corticosterone pathway; (2) EPA may attenuate IL-1 effects via inhibiting PLA2 activities, which blocks PGE2 stimulation of corticosterone. Using an in vivo microdialysis method, the present study showed that IL-1 administration significantly increased extracellular levels of DA, and its metabolites 3,4-dihydroxyphenylacetic acid, [corrected] and homovanillic acid [corrected] in the shell of the NAc. IL-1 also increased blood concentration of corticosterone and PGE2, and increased the activities of cytosolic and secretory [corrected] PLA2. IL-1-induced changes were significantly attenuated by EPA treatment. Furthermore, glucocorticoid [corrected] receptor antagonist mifepristone (RU486) pretreatment significantly blocked IL-1-induced changes in DA and metabolites. Quinacrine, [corrected] a PLA2 antagonist significantly blocked IL-1-induced [corrected] increase in PGE2 and corticosterone concentrations. These results demonstrated the hypotheses that IL-1 effects may be via PLA2-PGE2-corticosterone pathway and EPA attenuated IL-1 effects may be through the suppression of PLA2 expression, which then reduced PGE2 synthesis and corticosterone secretion.
此前，我们曾报道白细胞介素-1β（IL-1）可诱导伏隔核（NAc）核心区多巴胺能（DA）和5-羟色胺能系统发生变化。我们还证实，n-3脂肪酸二十碳五烯酸乙酯（EPA）可显著减轻IL-1给药诱导的应激和焦虑样行为、皮质酮浓度以及外周炎症反应。与核心区相比，壳区更多地参与情绪、应激和精神疾病。然而，炎症与壳区DA系统功能之间的关系尚未得到研究。由于磷脂酶（PL）A2是花生四烯酸-类花生酸-前列腺素（PG）E2途径中的关键酶，且NAc DA系统的变化与糖皮质激素刺激有关；因此，本研究的假设为：（1）IL-1诱导壳区DA神经传递变化可能通过PLA2-PGE2-皮质酮途径；（2）EPA可能通过抑制PLA2活性来减弱IL-1的作用，从而阻断PGE2对皮质酮的刺激。本研究采用体内微透析方法，结果显示，给予IL-1可显著提高NAc壳区细胞外DA及其代谢产物3,4-二羟基苯乙酸和高香草酸的水平。IL-1还可提高皮质酮和PGE2的血浓度，并增加胞质型和分泌型PLA2的活性。EPA处理可显著减弱IL-1诱导的变化。此外，糖皮质激素受体拮抗剂米非司酮（RU486）预处理可显著阻断IL-1诱导的DA及其代谢产物的变化。PLA2拮抗剂喹吖因可显著阻断IL-1诱导的PGE2和皮质酮浓度升高。这些结果证实了以下假设：IL-1的作用可能通过PLA2-PGE2-皮质酮途径，而EPA减弱IL-1的作用可能是通过抑制PLA2表达，进而减少PGE2合成和皮质酮分泌。
