GLUT12 Expression in Brain of Mouse Models of Alzheimer’s Disease
The brain depends on glucose as a source of energy. This implies the presence of glucose transporters, being GLUT1 and GLUT3 the most relevant. Expression of GLUT12 is found in mouse and human brain at low levels. We previously demonstrated GLUT12 upregulation in the frontal cortex of aged subjects that was even higher in aged Alzheimer’s disease (AD) patients. However, the cause and the mechanism through which this increase occurs are still unknown. Here, we aimed to investigate whether the upregulation of GLUT12 in AD is related with aging or Aβ deposition in comparison with GLUT1, GLUT3, and GLUT4. In the frontal cortex of two amyloidogenic mouse models (Tg2576 and APP/PS1) GLUT12 levels were increased. Contrary, expression of GLUT1 and GLUT3 were decreased, while GLUT4 did not change. In aged mice and the senescence-accelerated model SAMP8, GLUT12 and GLUT4 were upregulated in comparison with young animals. GLUT1 and GLUT3 did not show significant changes with age. The effect of β-amyloid (Aβ) deposition was also evaluated in Aβ peptide i.c.v. injected mice. In the hippocampus, GLUT12 expression increased whereas GLUT4 was not modified. Consistent with the results in the amyloidogenic models, GLUT3 and GLUT1 were downregulated. In summary, Aβ increases GLUT12 protein expression in the brain pointing out a central role of the transporter in AD pathology and opening new perspectives for the treatment of this neurodegenerative disease.
KeywordsAging Alzheimer’s disease Beta-amyloid Brain GLUT
EG-I, MS, MC-T, MJR, and MPL designed the experiments. EG-I and MS carried out the experiments. MPL and EG-I analyzed the data and wrote the manuscript. MS, MC-T, AGO, XE, and MJR provided the animals and samples. All authors participated in the critical review and approved the final version.
Eva Gil-Iturbe was supported by a fellowship from the Nutrition Research Centre University of Navarra. This work was funded by grants from Instituto de Salud Carlos III FIS 14/01244 to MC-T and AGO; and FIS PI 13/00858 to MJR.
Compliance with Ethical Standards
All experiments were performed according to international animal care guidelines and with the approval of the Ethics Committee for Animal Experimentation of the University of Navarra (Protocols 022-14, 090-13 and 115-18).
Conflict of Interest
The authors declare that they have no conflict of interest.
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