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. 2008 Jul;38(4):396-406.
doi: 10.1007/s10519-008-9208-1. Epub 2008 May 7.

Deletion of glucose transporter GLUT8 in mice increases locomotor activity

S Schmidt  1 , V Gawlik, S M Hölter, R Augustin, A Scheepers, M Behrens, W Wurst, V Gailus-Durner, H Fuchs, M Hrabé de Angelis, R Kluge, H-G Joost, A Schürmann
Affiliations

Deletion of glucose transporter GLUT8 in mice increases locomotor activity

S Schmidt et al. Behav Genet. 2008 Jul.

Abstract

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.

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Figures

Fig. 1
Fig. 1
Analyses of GLUT8 expression in mouse brains by in situ hybridization. (a) 20 μm cross-sections of mouse brains were hybridized with GLUT8-specific digoxigenin-labeled riboprobes and stained by standard colorimetry as described in Material and methods. Signals were obtained with the antisense probes (left panel), whereas sections of Slc2a8 −/− brains did not show signals (right panel). As an additional control, brain sections from wild-type mice were incubated with probes corresponding to the sense strands of GLUT8 (middle panels). AA, amygdala; CO, cortex; HP, hippocampus; TH, thalamus; HT, hypothalamus. (b) Genotyping of mice was performed by PCR as described in Material and methods. (c) Slc2a8 mRNA levels of Slc2a8 +/+ and Slc2a8 −/− littermates in hippocampus, amygdala, and hypothalamus were assayed by quantitative real time-PCR (qRT-PCR) as described in Material and methods. (d) Immunohistochemical detection of GLUT8 in the hippocampus, cortex, and thalamus. Sections of the brain from Slc2a8 +/+ and Slc2a8 −/− mice were fixed with paraformaldehyde and incubated with the anti-GLUT8 antiserum. The immunostaining was performed with peroxidase-conjugated secondary antibody as described in Material and methods
Fig. 2
Fig. 2
Hyperactivity of Slc2a8 −/− mice detected in the modified hole board (mHB) test. Slc2a8 +/+ and Slc2a8 −/− mice at the age of 8 weeks were monitored in the mHB test for 5 min. (a) Mean velocity, (b) total distance traveled, (c) line crossings, and (d) turns of Slc2a8 −/− males (n = 15) were compared to Slc2a8 +/+ males (n = 15). Data are presented as mean + S.E.M. *P < 0.05; **P < 0.01; ***P < 0.001
Fig. 3
Fig. 3
Hyperactivity of Slc2a8 −/− mice detected in the home cage. (a) Monitoring locomotor activity and (b) voluntary physical activity of 6 weeks old Slc2a8 +/+ and Slc2a8 −/− males. Cages were equipped with an infrared detector and voluntary running wheels, and activities of mice were monitored after an adaptation period of 2 days. Means of activities during the indicated time spans were calculated for each individual animal for the dark and light phase over a period of 24 h. Data are presented as mean + S.E.M. of 9 Slc2a8 +/+ and 12 Slc2a8 −/− mice. **P < 0.01; ***P < 0.001
Fig. 4
Fig. 4
Exploration activity of Slc2a8 −/− mice. Slc2a8 +/+ and Slc2a8 −/− mice at the age of 8 weeks were monitored in the mHB test for 5 min with the focus on exploration of holes (a) and objects (B)
Fig. 5
Fig. 5
Behavior of Slc2a8 −/− mice on the board. Slc2a8 +/+ and Slc2a8 −/− mice at the age of 8 weeks were monitored in the mHB for 5 min. (a) board entries, (b) percentage of time spent on the board, (c) grooming, and (d) defecation of Slc2a8 −/− males (n = 15) were compared to Slc2a8 +/+ males (n = 15). Data are presented as mean + S.E.M. **P < 0.01
Fig. 6
Fig. 6
Exploratory strategy of Slc2a8 −/− mice. Slc2a8 +/+ and Slc2a8 −/− mice at the age of 8 weeks were monitored in the mHB for 5 min. (a) rearings on board, (b) rearings on box and (c) latency to stretched body posture of 8 weeks old Slc2a8 +/+ males (n = 15) were compared to Slc2a8 −/− males (n = 15). Data are presented as mean + S.E.M. *P < 0.05; **P < 0.01
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