Deletion of Glucose Transporter GLUT8 in Mice Increases Locomotor Activity

Transport of glucose into neuronal cells is predominantly mediated by the glucose transporters GLUT1 and GLUT3. In addition, GLUT8 is expressed in some regions of the brain. By in situ hybridization we detected GLUT8-mRNA in hippocampus, thalamus, and cortex. However, its cellular and physiological function is still unknown. Thus, GLUT8 knockout (Slc2a8−/−) mice were used for a screening approach in the modified hole board (mHB) behavioral test to analyze the role of GLUT8 in the central nervous system. Slc2a8−/− mice showed increased mean velocity, total distance traveled and performed more turns in the mHB test. This hyperactivity of Slc2a8−/− mice was confirmed by monitoring locomotor activity in the home cage and voluntary activity in a running wheel. In addition, Slc2a8−/− mice showed increased arousal as indicated by elevated defecation, reduced latency to the first defecation and a tendency to altered grooming. Furthermore, the mHB test gave evidence that Slc2a8−/− mice exhibit a reduced risk assessment because they performed less rearings in an unprotected area and showed significantly reduced latency to stretched body posture. Our data suggest that behavioral alterations of Slc2a8−/− mice are due to dysfunctions in neuronal processes presumably as a consequence of defects in the glucose metabolism

Insights into cognitive aging and Alzheimer’s disease using amyloid PET and structural MRI scans

Positron emission tomography using amyloid binding ligands, labeled with carbon-11 and fluorine-18, (Amyloid PET) has been used to understand the relationship between amyloid deposition in the brain, neurodegeneration and the development of mild cognitive impairment and dementia. Structural MRI has been used to identify morphological changes in the brain which may relate to the cause(s) of cognitive impairment, including infarcts, space-occupying lesions, hydrocephalus and the patterns of atrophy which are characteristic of various neurodegenerative diseases. These two imaging biomarkers have also played an important role in revealing the sequence of cerebral amyloid deposition, neurodegeneration and cognitive impairment. Although there may not be a direct relationship between amyloid deposition and brain atrophy or cognitive deficits, the presence of both amyloid deposition on PET and neurodegeneration on MRI has been associated with accelerated cognitive decline. The main focus of this article is to summarize some of the insights gained using these two imaging methods individually and in combination to better understand the biological bases of normal aging and age-associated cognitive impairment