Expression of the hexose transporters GLUT1 and GLUT2 during the early development of the human brain

doi:10.1016/S0006-8993(99)01078-1

Brain Research

Volume 824, Issue 1, 3 April 1999, Pages 97-104

https://doi.org/10.1016/S0006-8993(99)01078-1 Get rights and content

Abstract

We used immunohistochemistry with anti-glucose transporter antibodies to document the presence of facilitative hexose transporters in the fetal human brain. GLUT1 is expressed in all regions of the fetal brain from ages 10 to 21 weeks. GLUT1 was present in the endothelial cells of the brain capillaries, the epithelial cells of the choroid plexus and neurons. High expression of GLUT2 was observed in the granular layer of the cerebellum in brains 21 weeks old, but GLUT2 immunoreactivity was absent at earlier stages. GLUT3 and GLUT4 immunoreactivities were absent at all stages studied. GLUT5 immunoreactivity was evident only in the cerebellar region of 21-week old fetal brains. We conclude that GLUT1 plays a fundamental role in early human brain development. The data also suggest that the cerebellum of the developing brain has the capacity to transport fructose, a substrate that has not been previously identified as a source of metabolic energy in the adult human brain.

Introduction

The brain is isolated from systemic circulation by the blood–brain barrier (BBB). The metabolic activity of the brain is dependent on a continuous supply of glucose, and neuronal function is exquisitely sensitive to variations in concentrations of glucose in the brain 1, 10, 24, 25. Blood glucose crosses the BBB through facilitative hexose transporters (GLUTs) 9, 15, 19. Five glucose transporters, GLUT1 to GLUT5, have been molecularly cloned 2, 16, 17, 22, 31, 33. In the adult brain, GLUT1 is highly expressed in both the luminal and the abluminal membranes of the endothelial cells of brain capillaries, and is also present in the neuronal and glial cells of the adult brain 9, 15, 21, 26. Neurons express high levels of GLUT3, a high affinity glucose transporter 11, 12, 20, 23, 28. There is also evidence suggesting the presence of GLUT2, GLUT4, and GLUT5 in the adult brain 5, 18, 27.

In rat and mouse fetal brain, GLUT1 is highly expressed in neuroectodermal cells, in endothelial cells, in the epithelial cells of the choroid plexus and in the ependymal tanycytes 3, 4, 7, 13, 14, 29, 30, 34. No similar information regarding the expression of hexose transporters is available for the fetal human brain. Studies performed in humans failed to reveal the presence of proteins immunoreactive with anti-glucose transporters in the early fetal brain [21].

We studied the expression of hexose transporters during the early development of the human brain. Here, we provide immunohistochemical evidence indicating that GLUT1 is widely expressed during the early development of the fetal human brain. We also found high expression of GLUT2, and low expression of GLUT5, in the cerebellum during the latest stage of development of the fetal brain.

Section snippets

Material and methods

The brains of 15 human fetuses (10–21 weeks old) were obtained from the Pathology Service at the Regional Hospital in Temuco, Chile. Therapeutic abortions were performed for reasons other than Central Nervous System disease. Routine pathological analysis revealed no evidence of malformation or other abnormalities in these fetal brains. Each fetus was obtained and immersed in formaline for 2 h. Afterward, the brain was removed and fixed in Bouin solution at room temperature, dehydrated in graded

Results

We examined the expression of the facilitative hexose transporters GLUT1 to GLUT5 in brains of 10- to 21-week old human fetuses using a panel of anti-peptide antibodies specific for each transporter isoform. GLUT1 immunoreactive material was present in the endothelial cells of the capillaries, the choroid plexus, and the pineal gland cells at all developmental stages examined (Fig. 1Fig. 2). GLUT1 immunoreactivity was high in the endothelial cells (Fig. 1A–B). The erythrocytes present in the

Discussion

The immunohistochemical data indicate that the glucose transporter GLUT1 is expressed at high levels during the early stages of the development of the human fetal brain. GLUT1 was found in all regions of the brain, including the endothelial cells of the brain capillaries, the epithelial cells of the choroid plexus, the ependymal cells and in neurons. The data also indicate abundant expression of the low affinity glucose–fructose transporter GLUT2, and low expression of the high affinity

Acknowledgements

The authors thank Ms. Marı́a de la Luz Pascal and Mr. Jorge Seguel for their expert technical support, and Mr. Hernan Montecinos for his support in the early phases of this work. The support and encouragement of Drs. Carlos Figueroa, Juan Carlos Vera, and David W. Golde is kindly appreciated. This work was partially supported by grant 1980130 from FONDECYT, Chile and grant 96035001-11 from the Dirección de Investigación, Universidad de Concepción.

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Research reportExpression of the hexose transporters GLUT1 and GLUT2 during the early development of the human brain

Abstract

Introduction

Section snippets

Material and methods

Results

Discussion

Acknowledgements

Cell

Mol. Cell. Neurosci.

Biochem. Biophys. Res. Commun.

Neuroscience

Brain Res. Dev. Brain Res.

J. Biol. Chem.

J. Biol. Chem.

Mol. Cell. Endocrinol.

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Cell

Specialized properties and solute transport in brain capillaries

Annu. Rev. Physiol.

Subcellular distribution of glucose transporter (GLUT-1) during development of the blood–brain barrier in rats

Cell Tissue Res.

Pattern of glucose transporter (Glut 1) expression in embryonic brains is related to maturation of blood–brain barrier tightness

Dev. Dyn.

Developmental regulation of the distribution of rat brain insulin-insensitive (Glut 1) glucose transporter

Endocrinology

Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression

J. Clin. Invest.

Research report
Expression of the hexose transporters GLUT1 and GLUT2 during the early development of the human brain