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Deletion of glucose transporter GLUT8 in mice increases locomotor activity.

Schmidt S, Gawlik V, Hölter SM, Augustin R, Scheepers A, Behrens M, Wurst W, Gailus-Durner V, Fuchs H, Hrabé de Angelis M, Kluge R, Joost HG, Schürmann A - Behav. Genet. (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, Nuthetal, Germany.

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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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
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Fig2: 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

Mentions: To analyze the unconditioned behavior of Slc2a8−/− mice in comparison to their wild-type littermates the mHB test was used. This test is described to determine a variety of behavioral dimensions in only one test. In the mHB test, 8 weeks old Slc2a8−/− males were hyperactive in comparison to their wild-type littermates. Slc2a8−/− mice showed significantly (P < 0.01) increased mean velocity (Fig. 2a), and total distance traveled (P < 0.01; Fig. 2b). In addition, Slc2a8−/− mice displayed increased number of line crossings (P < 0.001; Fig. 2c) and performed more turns (P < 0.05; Table 1). To further address the role of neuronal GLUT8 for activity we monitored the locomotor activity in the home cage after a 48 h adaptation period of another set of animals. As shown in Fig. 3a, 6 weeks old Slc2a8−/− males exhibited significantly (P < 0.01) increased locomotor activity during the dark phase and in the total 24 h period (P < 0.01). Likewise, voluntary activity in the running wheel was significantly higher in Slc2a8−/− mice than in Slc2a8+/+ controls both in the dark phase (P < 0.001) and in the total 24 h period (P < 0.001 Fig. 3b). During the light phase, neither general locomotor or running wheel activity was different between the genotypes.Fig. 2


Deletion of glucose transporter GLUT8 in mice increases locomotor activity.

Schmidt S, Gawlik V, Hölter SM, Augustin R, Scheepers A, Behrens M, Wurst W, Gailus-Durner V, Fuchs H, Hrabé de Angelis M, Kluge R, Joost HG, Schürmann A - Behav. Genet. (2008)

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
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2480596&req=5

Fig2: 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
Mentions: To analyze the unconditioned behavior of Slc2a8−/− mice in comparison to their wild-type littermates the mHB test was used. This test is described to determine a variety of behavioral dimensions in only one test. In the mHB test, 8 weeks old Slc2a8−/− males were hyperactive in comparison to their wild-type littermates. Slc2a8−/− mice showed significantly (P < 0.01) increased mean velocity (Fig. 2a), and total distance traveled (P < 0.01; Fig. 2b). In addition, Slc2a8−/− mice displayed increased number of line crossings (P < 0.001; Fig. 2c) and performed more turns (P < 0.05; Table 1). To further address the role of neuronal GLUT8 for activity we monitored the locomotor activity in the home cage after a 48 h adaptation period of another set of animals. As shown in Fig. 3a, 6 weeks old Slc2a8−/− males exhibited significantly (P < 0.01) increased locomotor activity during the dark phase and in the total 24 h period (P < 0.01). Likewise, voluntary activity in the running wheel was significantly higher in Slc2a8−/− mice than in Slc2a8+/+ controls both in the dark phase (P < 0.001) and in the total 24 h period (P < 0.001 Fig. 3b). During the light phase, neither general locomotor or running wheel activity was different between the genotypes.Fig. 2

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, Nuthetal, Germany.

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.

Show MeSH
Related in: MedlinePlus