Selective alteration in blood-brain barrier and insulin transport in iron-deficient rats.
Nutritional iron deficiency induced in rats causes a significant reduction in level of brain nonheme iron and is accompanied by selective reduction of dopamine D2 receptor Bmax. Our previous studies have clearly demonstrated that these alterations can be restored to normal by supplementation with ferrous sulfate; however, neither brain nonheme iron level nor dopamine D2 receptor Bmax can be increased beyond control values even after long-term iron therapy. The possibility that iron deficiency can induce the breakdown of the blood-brain barrier (BBB) was examined. A 70 and 100% increase in brain uptake index (BUI) for L-glucose and insulin, respectively, were noted in iron-deficient rats. However, the BUI for valine was decreased by 40%, and those for L-norepinephrine and glycine were unchanged. In addition, it was demonstrated that in normal rats insulin is transported into the brain. The data show that iron deficiency selectively affects the integrity of the BBB for insulin, glucose, and valine transport. Whether the effect of iron deficiency on the BBB is at the level of the capillary endothelial cell tight junction is not yet known. However, this study has shown that an important nutritional disorder (iron-deficiency anemia) has a profound effect on the BBB and brain function.
Ben-Shachar
D
D
Department of Pharmacology, Rappaport Family Research Institute, Technion-Faculty of Medicine, Haifa, Israel.
Yehuda
S
S
Finberg
J P
JP
Spanier
I
I
Youdim
M B
MB
D000747:Anemia, Hypochromic / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism; D017448:Receptors, Dopamine D2; D014633:Valine / Q000378:metabolism
D007328:Insulin; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D014633:Valine; D005947:Glucose; D005998:Glycine; D009638:Norepinephrine