GFAP expression levels are associated with brain glucose metabolism in a rat model of Alzheimer’s disease

Abstract

AbstractBackgroundGlial Fibrillary Acidic Protein (GFAP) is an intermediate filament expressed almost exclusively in astrocytes, and it is usually overexpressed in reactive astrocytes. We have previously shown that astrocytes play a critical role in brain energy metabolism and are significant contributors to the [18F]FDG‐PET signal. The cortex is majorly composed of glial cells, whereas the cerebellum is predominantly composed of neurons. In light of this, whether GFAP levels in the brain tissue are associated with [18F]FDG‐PET signal remains unknown. Thus, we aimed to investigate the associations between cortical and cerebellar GFAP levels with brain glucose metabolism in a rat model of Alzheimer’s disease.MethodsBrain metabolism of ten‐month‐old TgF344‐AD (n=8) and wild‐type (WT,n=6) rats was assessed with [18F]FDG‐PET. Then, GFAP RNA levels were quantified in the frontal cortex (CXF), temporoparietal cortex (CXTP), and cerebellum (CB) using qRT‐PCR. The [18F]FDG‐PET standardized uptake ratio (SUVr) was calculated using pons as the reference region. T‐tests were used to assess the differences between groups in GFAP RNA expression levels and regional brain [18F]FDG‐PET. Comparisons were conducted using t‐statistical analyses at voxel level (RMINC). Differences were considered statistically significant at p<0.05 (t>2).ResultsNo differences between groups were found in the whole brain FDG metabolism or regions of interest (CXF, CXTP, and CB;t(13)<2). At the voxel level, we identified small cortical hypermetabolic clusters in the TgF344‐AD rats (t(13)=5.55, local maxima). The GFAP RNA was increased in the CXTP of TgF344‐AD rats (p=0.001). No significant differences were found between groups in GFAP RNA levels in other brain regions evaluated. Interestingly, we found positive correlations between [18F]FDG‐PET metabolism and the GFAP RNA expression in the CXTP (local maxima, t(13)=8.33;Fig.1a) and CXF (local maxima, t(13)=4.82;Fig.1b). By contrast, [18F]FDG metabolism did not associate with GFAP RNA expression levels in the CB (t(13)<2;Fig.1c).ConclusionGFAP RNA levels were increased in the CXTP of TgF344‐AD rats, which may indicate early astrocyte reactivity. GFAP RNA expression was associated with [18F]FDG metabolism only in cortical regions, suggesting that astrocytes may have major roles in cortical glucose uptake, but not in cerebellum.