Distribution, regulation and colocalization of the genes encoding the EP2‐ and EP4‐PGE2 receptors in the rat brain and neuronal responses to systemic inflammation
Distribution, regulation and colocalization of the genes encoding the EP2‐ and EP4‐PGE2 receptors in the rat brain and neuronal responses to systemic inflammation
复制标题
编码 EP2- 和 EP4-PGE2 受体的基因在大鼠大脑中的分布、调节和共定位以及对全身炎症的神经反应
DOI：
--
复制
发表时间：
1999
影响因子：
3.4
通讯作者：
S. Rivest
中科院分区：
文献类型：
--
作者：
Ji Zhang;S. Rivest
目前认为，E2型前列腺素（PG）在将从循环免疫因子接收的信息传递到脑实质细胞中起关键作用。虽然PGE 2基本上是由血脑屏障细胞合成的，但其受体亚型在神经元元件内的组织和调节仍然未知。在本研究中，静脉内（i. v.）注射内毒素脂多糖（LPS）或重组大鼠白细胞介素-1 β（IL-1β），肌肉内（i.m.）注射姜黄素作为不同的全身免疫刺激模型。在损伤后的不同时间（30分钟至24小时）对大鼠进行灌注，将其大脑切割并与全长大鼠cRNA探针杂交。 完成双标记程序以确定细胞表型和活性。在基础条件下，发现EP 2和EP 4受体在整个脑中有非常明显的分布;在终纹床核（BNST）、外侧隔、穹窿下器（SFO）、下丘脑腹内侧核（VMH）、杏仁中央核（CeA）、蓝斑（LC）和最后区（AP）检测到2型杂交信号，而在基础条件下，腹侧隔/前视前区、大细胞室旁核（PVN）、视上核、臂旁核、LC、孤束核（NTS）和延髓腹外侧区（VLM）显示出中等至强水平的EP 4 mRNA。在全身性炎症挑战过程中，在选择性区域和神经元群体中检测到编码EP 2和EP 4受体的基因的上调。最引人注目的是静脉注射LPS和IL-1β后，小细胞PVN的促肾上腺皮质激素释放因子（CRF）神经元内EP 4亚型的稳健转录激活，以及局部静脉注射LPS和IL-1β后，小细胞PVN的促肾上腺皮质激素释放因子（CRF）神经元内EP 4亚型的转录激活。侵略这些内分泌下丘脑的神经元以及许多自主神经相关核的神经元被促炎细胞因子激活，因为它们对Fos核蛋白具有免疫反应性（ir）。EP 4转录物也存在于LC、NTS和VLM的活化的儿茶酚胺能神经元中，尽管只有A1细胞组显示EP 4转录响应于循环IL-1β而增加。此外，全身免疫原性损伤引起CeA，SFO，AP和软脑膜中EP 2 mRNA水平的显著增加。这些数据提供了在基础和免疫激发条件下整个大鼠大脑中EP 2和EP 4表达的不同模式，并支持EP 4亚型在介导PGE 2对不同自主神经和神经内分泌功能的影响中的可能作用。IL-1β处理动物的各种EP 4神经元群体中Fos-ir核的存在清楚地支持了这一概念，并表明全身炎症期间神经元反应的选择性可能取决于大脑关键结构中特异性PGE 2受体的表达。
It is currently believed that prostaglandin (PG) of E2 type plays a crucial role in transferring the information received from circulating immune factors to brain parenchymal cells. Although PGE2 is synthesized quite essentially by cells of the blood–brain barrier, the organization and regulation of its receptor subtypes within neuronal elements remain unknown. In this study, intravenous (i.v.) injection of the endotoxin lipopolysaccharide (LPS) or recombinant rat interleukin‐1β (IL‐1β), and intramuscular (i.m.) injection of turpentine were used as different models of systemic immune stimuli. Rats were perfused at various times after the insults (30 min to 24 h), their brains cut and hybridized with full‐length rat cRNA probes. Double‐labelling procedures were accomplished to determine the cellular phenotype and activity. A very distinct distribution of both EP2 and EP4 receptors was found across the brain under basal conditions; the hybridization signal for the type 2 was detected in the bed nucleus of the stria terminalis (BNST), lateral septum, subfornical organ (SFO), ventromedial hypothalamic nucleus (VMH), central nucleus of the amygdala (CeA), locus coeruleus (LC) and the area postrema (AP), whereas the ventral septal/anterior preoptic area, the magnocellular paraventricular nucleus (PVN), supraoptic nucleus, parabrachial nucleus, LC, the nucleus of the solitary tract (NTS) and the ventrolateral medulla (VLM) exhibited moderate to strong levels for the EP4 mRNA under basal conditions. Upregulation of the genes encoding EP2 and EP4 receptors was detected in selective regions and neuronal populations during systemic inflammatory challenges. The most dramatic one being the robust transcriptional activation of the EP4 subtype within corticotropin‐releasing factor (CRF) neurons of the parvocellular PVN following i.v. LPS and IL‐1β injection, and the localized i.m. aggression. These neurons of the endocrine hypothalamus as well as those of numerous autonomic‐related nuclei were activated by the proinflammatory cytokine, as they were immunoreactive (ir) to Fos nuclear protein. The EP4 transcript was also present in activated catecholaminergic neurons of the LC, NTS and VLM, although only the A1 cell group exhibited an increase in EP4 transcription in response to circulating IL‐1β. Moreover, the systemic immunogenic insults caused a significant increase in the EP2 mRNA levels in the CeA, SFO, AP and the leptomeninges. These data provide a distinct pattern of EP2 and EP4 expression throughout the rat brain under both basal and immune‐challenged conditions, and underlie the possible role of the EP4 subtype in mediating the effects of PGE2 on different autonomic and neuroendocrine functions. The presence of Fos‐ir nuclei in various populations of EP4 neurons of IL‐1β‐treated animals clearly supports this concept and suggests that the selectivity of the neuronal response during systemic inflammation may depend on the expression of specific PGE2 receptors in key structures of the brain.
DOI：
10.1152/ajpregu.1998.274.3.r783
发表时间：
1998-03-01
影响因子：
2.8
作者：
Scammell, TE;Griffin, JD;Saper, CB
通讯作者：
Saper, CB
促肾上腺皮质激素释放激素基因中的 cAMP 反应元件通过去极化介导转录调节。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Guardiola-Diaz,HM;Boswell,C;Seasholtz,AF
通讯作者：
Seasholtz,AF
前列腺素 E2 的中枢给药可抑制体外细胞免疫反应。
DOI：
10.1152/ajpregu.1995.269.1.r92
发表时间：
1995
期刊：
The American journal of physiology.
影响因子：
--
作者：
Rassnick,S;Zhou,D;Rabin,BS
通讯作者：
Rabin,BS