Chronic hypoxia causes opposite effects on glucose transporter 1 mRNA in mature versus immature rat brain

Abstract

We have shown previously that chronic hypoxia can regulate the expression of membrane proteins. Since there are virtually no glucose stores in the brain and glucose transport can be rate-limiting during stress, the role of glucose transporters becomes crucial for cell survival under stress. In the present study, we asked whether mRNA levels for glucose transporter 1 (GT1), which is expressed in a variety of cells in the brain, especially in the microvessels for glucose transport from blood vessels to brain, change in response to chronic hypoxia. Because major developmental changes occur in the rat CNS in-utero and in the first few weeks postnatally, we studied brain GT1 mRNA using Northern blot analysis at different ages after exposure of fetuses (from embryonic day 10 to birth), developing rats (from birth to 30 day old) or adult rats (from 90 to 120 day old) to hypoxia (Fractional inspired O 2 9%). Our data show that (i) GT1 mRNA level was much lower in the newborn that in the adult and increased with age; (ii) chronic hypoxia caused a decrease of ∼65% in GT1 mRNA in adult brain but induced an increase in fetal (more than 50%) and developing (∼80%) rats and (iii) the response of housekeeping gene (glyceraldehyde 3-phosphate dehydrogenase) was not similar to that of GT1, suggesting that the changes of GT1 mRNA are specific to glucose transporter. We believe that the increase in GT1 mRNA with age is a reflection of an increase in O 2 and glucose consumption in brain tissue and that the differential response of GT1 mRNA to long term O 2 deprivation is a reflection of differential reliance on various intermediary metabolic pathways in the immature versus the mature rat brain.