SDF-1alpha/CXCL12 enhances GABA and glutamate synaptic activity at serotonin neurons in the rat dorsal raphe nucleus.
SDF-1alpha/CXCL12 enhances GABA and glutamate synaptic activity at serotonin neurons in the rat dorsal raphe nucleus.
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DOI：
10.1016/j.neuropharm.2009.08.022
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发表时间：
2010-02
影响因子：
4.7
通讯作者：
Kirby, Lynn G.
中科院分区：
文献类型：
--
作者：
Heinisch, Silke;Kirby, Lynn G.
血清素（5-羟色胺; 5-HT）系统在抑郁症中具有明确的作用。最近的报告描述了情绪免疫障碍的共病，表明免疫成分也可能有助于抑郁症的发病机制。趋化因子，介导白细胞运输的免疫蛋白，及其受体广泛分布于脑中，介导神经元模式，并调节各种神经病理。本研究的目的是通过解剖学和电生理技术研究趋化因子基质细胞衍生因子-1 α/CXCL 12及其受体CXCR 4对大鼠中缝背核（DRN）5-羟色胺系统的神经解剖关系和功能影响。免疫组织化学分析表明，超过70%的5-HT神经元与CXCL 12和CXCR 4共定位。在亚细胞水平，CXCL 12定位于整个细胞质，而CXCR 4集中于5-HT神经元的外膜和突起。CXCL 12和CXCR 4也共定位于单个DRN细胞上。此外，电生理研究表明，CXCL 12去极化的5-HT神经元间接通过谷氨酸突触输入。CXCL 12还增强自发抑制性和兴奋性突触后电流（sIPSC和sEPSC）的频率。CXCL 12浓度依赖性地增加诱发的IPSC振幅，并降低诱发的IPSC配对脉冲比选择性地在5-HT神经元，CXCR 4拮抗剂AMD 3100阻断的效果。这些数据表明CXCL 12在突触前增强5-HT DRN神经元的GABA和谷氨酸释放。免疫组织化学分析进一步显示CXCR 4定位于DRN GABA神经元，为CXCL 12对GABA释放的作用提供了解剖学基础。因此，CXCL 12通过GABA和谷氨酸突触传入间接调节5-HT神经传递。未来靶向CXCL 12和其他趋化因子的疗法可能治疗血清素相关的情绪障碍，特别是免疫受损个体经历的抑郁症。
The serotonin (5-hydroxytryptamine; 5-HT) system has a well-characterized role in depression. Recent reports describe comorbidities of mood-immune disorders, suggesting an immunological component may contribute to the pathogenesis of depression as well. Chemokines, immune proteins which mediate leukocyte trafficking, and their receptors are widely distributed in the brain, mediate neuronal patterning, and modulate various neuropathologies. The purpose of this study was to investigate the neuroanatomical relationship and functional impact of the chemokine stromal cell-derived factor-1α/CXCL12 and its receptor, CXCR4, on the serotonin dorsal raphe nucleus (DRN) system in the rat using anatomical and electrophysiological techniques. Immunohistochemical analysis indicates that over 70% of 5-HT neurons colocalize with CXCL12 and CXCR4. At a subcellular level, CXCL12 localizes throughout the cytoplasm whereas CXCR4 concentrates to the outer membrane and processes of 5-HT neurons. CXCL12 and CXCR4 also colocalize on individual DRN cells. Furthermore, electrophysiological studies demonstrate CXCL12 depolarization of 5-HT neurons indirectly via glutamate synaptic inputs. CXCL12 also enhances the frequency of spontaneous inhibitory and excitatory postsynaptic currents (sIPSC and sEPSC). CXCL12 concentration-dependently increases evoked IPSC amplitude and decreases evoked IPSC paired-pulse ratio selectively in 5-HT neurons, effects blocked by the CXCR4 antagonist AMD3100. These data indicate presynaptic enhancement of GABA and glutamate release at 5-HT DRN neurons by CXCL12. Immunohistochemical analysis further shows CXCR4 localization to DRN GABA neurons, providing an anatomical basis for CXCL12 effects on GABA release. Thus, CXCL12 indirectly modulates 5-HT neurotransmission via GABA and glutamate synaptic afferents. Future therapies targeting CXCL12 and other chemokines may treat serotonin related mood disorders, particularly depression experienced by immune-compromised individuals.
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影响因子：
4.8
作者：
Callewaere, Celine;Fernette, Brigitte;Rostene, William
通讯作者：
Rostene, William
DOI：
10.1073/pnas.0602620103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Callewaere, Celine;Banisadr, Ghazal;Parsadaniantz, Stephane Melik
通讯作者：
Parsadaniantz, Stephane Melik
DOI：
10.1073/pnas.95.3.1283
发表时间：
1998-02-03
影响因子：
11.1
作者：
Goda, Y;Stevens, CF
通讯作者：
Stevens, CF
影响因子：
4.7
作者：
Bajetto, A;Bonavia, R;Schettini, G
通讯作者：
Schettini, G
DOI：
10.1196/annals.1296.005
发表时间：
2004-01-01
期刊：
STRESS: CURRENT NEUROENDOCRINE AND GENETIC APPROACHES
影响因子：
--
作者：
Abrams, JK;Johnson, PL;Lowry, CA
通讯作者：
Lowry, CA