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      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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          Abstract

          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 turnover 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 (>55years) 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 (Visit 1) and after 4weeks (Visit 2) of either IFN-alpha (n=17) or no treatment (n=14). Older patients treated with IFN-alpha exhibited a significantly greater increase in 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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          Author and article information

          Journal
          Brain Behav. Immun.
          Brain, behavior, and immunity
          Elsevier BV
          1090-2139
          0889-1591
          May 2015
          : 46
          Affiliations
          [1 ] Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
          [2 ] Coulter BME Biomedical Imaging Technology Center, Emory University School of Medicine, Atlanta, GA United States.
          [3 ] Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, United States.
          Article
          S0889-1591(14)00567-4 NIHMS651243
          10.1016/j.bbi.2014.12.004
          4414678
          25500218
          07c24126-e5df-4a99-b36d-608d037b746e
          History

          IFN-alpha,Inflammation,Motivation,Psychomotor speed,TNF,Aging,Basal ganglia,Cytokine,Glutamate

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