The chemokine SDF-1/CXCL12 modulates the firing pattern of vasopressin neurons and counteracts induced vasopressin release through CXCR4
The chemokine SDF-1/CXCL12 modulates the firing pattern of vasopressin neurons and counteracts induced vasopressin release through CXCR4
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DOI：
10.1073/pnas.0602620103
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发表时间：
2006-05-23
影响因子：
11.1
通讯作者：
Parsadaniantz, Stephane Melik
中科院分区：
文献类型：
--
作者：
Callewaere, Celine;Banisadr, Ghazal;Parsadaniantz, Stephane Melik
趋化因子在炎症中起关键作用。它们不仅在神经炎性疾病中表达，而且在不同的细胞类型中组成性表达，包括正常脑中的神经元，这表明它们可能充当神经元功能的调节剂。在这里，我们研究了趋化因子基质细胞衍生因子1（SDF-1）/CXCL 12可能的神经内分泌作用。我们证明了SDF-1及其受体CXCR 4与精氨酸加压素（AVP）在视上核（SON）和下丘脑室旁核的大细胞神经元和AVP投射到神经垂体的共定位。SON神经元的电生理记录表明SDF-1通过CXCR 4影响AVP神经元的电活动，导致AVP释放的变化。我们观察到SDF-1在体外可以减弱AVP释放的自动调节，在体内可以对抗血管紧张素II诱导的血浆AVP释放。此外，AVP释放的短期生理性增加由增强的血浆渗透压诱导，这是由1 M NaCl i. p.给药产生的，通过CXCR 4中心注射SDF-1类似地阻断。长期盐负荷引起的水平衡变化导致SDF-1和CXCR 4的减少，与SON中AVP免疫染色的减少平行。从这些数据中，我们证明了大脑中的趋化因子作用并不局限于炎症过程。我们建议在已知的AVP对其自身神经元的自调节之外，添加由SDF-1诱导的第二个自分泌系统，能够调节中枢AVP神经元的活性和释放。
Chemokines play a key role in inflammation. They are expressed not only in neuroinflammatory conditions, but also constitutively by different cell types, including neurons in the normal brain, suggesting that they may act as modulators of neuronal functions. Here, we investigated a possible neuroendocrine role of the chemokine stromal cell-derived factor 1 (SDF-1)/CXCL12. We demonstrated the colocalization of SDF-1 and its receptor CXCR4 with arginine vasopressin (AVP) in the magnocellular neurons of the supraoptic nucleus (SON) and the paraventricular hypothalamic nucleus and on AVP projections to the neurohypophysis. Electrophysiological recordings of SON neurons demonstrated that SDF-1 affects the electrical activity of AVP neurons through CXCR4, resulting in changes in AVP release. We observed that SDF-1 can blunt the autoregulation of AVP release in vitro and counteract angiotensin II-induced plasma AVP release in vivo. Furthermore, a short-term physiological increase in AVP release induced by enhanced plasma osmolarity, which was produced by the administration of 1 M NaCl i.p., was similarly blocked by central injection of SDF-1 through CXCR4. A change in water balance by long-term salt loading induced a decrease in both SDF-1 and CXCR4 parallel to that of AVP immunostaining in SON. From these data, we demonstrate that chemokine actions in the brain are not restricted to inflammatory processes. We propose to add to the known autoregulation of AVP on its own neurons, a second autocrine system induced by SDF-1 able to modulate central AVP neuronal activity and release.