Regional characterization of energy metabolism in the brain of normal and MPTP-intoxicated mice using new markers of glucose and phosphate transport.
The gibbon ape leukemia virus (GALV), the amphotropic murine leukemia virus (AMLV) and the human T-cell leukemia virus (HTLV) are retroviruses that specifically bind nutrient transporters with their envelope glycoproteins (Env) when entering host cells. Here, we used tagged ligands derived from GALV, AMLV, and HTLV Env to monitor the distribution of their cognate receptors, the inorganic phosphate transporters PiT1 and PiT2, and the glucose transporter GLUT1, respectively, in basal conditions and after acute energy deficiency. For this purpose, we monitored changes in the distribution of PiT1, PiT2 and GLUT1 in the cerebellum, the frontal cortex, the corpus callosum, the striatum and the substantia nigra (SN) of C57/BL6 mice after administration of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridinium (MPTP), a mitochondrial complex I inhibitor which induces neuronal degeneration in the striato-nigral network.The PiT1 ligand stained oligodendrocytes in the corpus callosum and showed a reticular pattern in the SN. The PiT2 ligand stained particularly the cerebellar Purkinje cells, while GLUT1 labelling was mainly observed throughout the cortex, basal ganglia and cerebellar gray matter. Interestingly, unlike GLUT1 and PiT2 distributions which did not appear to be modified by MPTP intoxication, PiT1 immunostaining seemed to be more extended in the SN. The plausible reasons for this change following acute energy stress are discussed.These new ligands therefore constitute new metabolic markers which should help to unravel cellular adaptations to a wide variety of normal and pathologic conditions and to determine the role of specific nutrient transporters in tissue homeostasis.
UMR Inserm U 930, CNRS FRE 2448, Université François Rabelais de Tours, F-37044 Tours, France.
Emmanuelle
E
Lagrue
Hiroyuki
H
Abe
Madakasira
M
Lavanya
Jawida
J
Touhami
Sylvie
S
Bodard
Sylvie
S
Chalon
Jean-Luc
JL
Battini
Marc
M
Sitbon
Pierre
P
Castelnau
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage*; D000818:Animals; D001692:Biological Transport; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015686:Gene Products, env / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000032:analysis* / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism; D017989:Leukemia Virus, Gibbon Ape / Q000235:genetics / Q000378:metabolism; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D011991:Receptors, Virus / Q000032:analysis* / Q000378:metabolism; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000032:analysis* / Q000378:metabolism
D015415:Biomarkers; D015686:Gene Products, env; D051272:Glucose Transporter Type 1; D008024:Ligands; D011991:Receptors, Virus; C493587:Slc20a1 protein, mouse; C493565:Slc20a2 protein, mouse; C495678:Slc2a1 protein, mouse; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine