Age-related increases in basal ganglia glutamate are associated with TNF, reduced motivation and decreased psychomotor speed during IFN-alpha treatment: Preliminary findings.
Age-related increases in basal ganglia glutamate are associated with TNF, reduced motivation and decreased psychomotor speed during IFN-alpha treatment: Preliminary findings.
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DOI：
10.1016/j.bbi.2014.12.004
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发表时间：
2015-05
影响因子：
15.1
通讯作者：
Miller, Andrew H.
中科院分区：
文献类型：
--
作者：
Haroon, Ebrahim;Felger, Jennifer C.;Woolwine, Bobbi J.;Chen, Xiangchuan;Parekh, Samir;Spivey, James R.;Hu, Xiaoping P.;Miller, Andrew H.
炎症诱导的中枢神经系统(CNS)代谢的改变主要集中在谷氨酸。在过高的浓度下，谷氨酸对胶质细胞和神经元具有毒性，炎性细胞因子通过阻止谷氨酸的再摄取和增加谷氨酸的释放来影响谷氨酸的代谢。在抑郁症中也发现谷氨酸增加，这是一种与炎症增加相关的疾病。我们小组的数据显示，接受炎性细胞因子干扰素-α治疗的患者基底节和背侧前扣带皮质谷氨酸水平升高。考虑到年龄增长与夸大的中枢神经系统炎症反应相关的数据，我们研究了年龄越大(55岁)是否会与干扰素-α诱导的中枢神经系统谷氨酸的增加相关。采用纵向设计，31例丙型肝炎患者在接受干扰素治疗(n=17)或不治疗(n=14)前(访1)和4周(访2)分别进行MRS、血液标本炎性标志物和行为学评估。接受干扰素治疗的老年患者在就诊1至就诊2期间，左侧基底节谷氨酸/肌酸比值(Glu/Cr)明显高于老年对照组和接受干扰素治疗和未治疗的年轻患者。此外，在接受α-干扰素治疗的老年患者和未接受治疗的患者中，Glu/Cr的增加与肿瘤坏死因子的增加、多维疲劳量表测量的动机减少以及在剑桥神经心理测试自动化电池上增加的选择运动时间有关。综上所述，这些初步数据支持这样的观点，即老年人可能与炎症相互作用，夸大炎症刺激对中枢神经系统谷氨酸和行为的影响。
Inflammation-induced alterations in central nervous system (CNS) metabolism have focused on glutamate. At excessive concentrations, glutamate is toxic to glia and neurons, and inflammatory cytokines have been shown to influence glutamate metabolism by blocking glutamate reuptake and increasing glutamate release. Increased glutamate has also been found in depression, a disorder associated with increased inflammation. Data by our group have shown increased glutamate as measured by magnetic resonance spectroscopy (MRS) in basal ganglia and dorsal anterior cingulate cortex of patients administered the inflammatory cytokine interferon (IFN)-alpha. Given data that increasing age is associated with an exaggerated CNS inflammatory response, we examined whether older age (>55 years) would be associated with a greater IFN-alpha-induced increase in CNS glutamate. Using a longitudinal design, 31 patients with hepatitis C virus (HCV) underwent MRS, blood sampling for inflammatory markers, and behavioral assessments before (Visit1) and after four weeks (Visit 2) of either IFN-alpha (n=17) or no treatment (n=14). Older patients treated with IFN-alpha exhibited a significantly increased glutamate from Visit 1 to Visit 2 as reflected by the glutamate/creatine ratio (Glu/Cr) in left basal ganglia compared to older controls and younger IFN-alpha-treated and untreated subjects. In addition, increased Glu/Cr in older but not younger IFN-alpha-treated and untreated patients was associated with increased tumor necrosis factor, reduced motivation as measured by the Multidimensional Fatigue Inventory and increased choice movement time on the Cambridge Neuropsychological Test Automated Battery. Taken together, these preliminary data support the notion that older age may interact with inflammation to exaggerate the effects of inflammatory stimuli on CNS glutamate and behavior.
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影响因子：
10.6
作者：
Miller, Andrew H.;Maletic, Vladimir;Raison, Charles L.
通讯作者：
Raison, Charles L.
影响因子：
5
作者：
Norden DM;Godbout JP
通讯作者：
Godbout JP
影响因子：
--
作者：
Capuron L;Pagnoni G;Drake DF;Woolwine BJ;Spivey JR;Crowe RJ;Votaw JR;Goodman MM;Miller AH
通讯作者：
Miller AH
影响因子：
10.6
作者：
Yuksel, Cagri;Oenguer, Dost
通讯作者：
Oenguer, Dost
影响因子：
4.4
作者：
Binesh, N;Kumar, A;Thomas, MA
通讯作者：
Thomas, MA