GLUT2 Immunoreactivity in Gomori-positive Astrocytes of the Hypothalamus

Abstract

S U M M A R YA specialized subtype of astrocyte, the Gomori-positive (GP) astrocyte, is unusually abundant and prominent in the arcuate nucleus of the hypothalamus. GP astrocytes possess cytoplasmic granules derived from degenerating mitochondria. GP granules are highly stained by Gomori's chrome alum hematoxylin stain, by the Perl's reaction for iron, or by toluidine blue. The source of the oxidative stress causing mitochondrial damage in GP astrocytes is uncertain, but such damage could arise from the oxidative metabolism of glucose transported into astrocytes by high-capacity GLUT2 glucose transporters. In accord with this hypothesis, the reported anatomical distribution of astrocytes staining positively for GLUT2 glucose transporters closely matches that of GP astrocytes. To examine whether or not these two staining procedures detect the same population of astrocytes, immunocytochemistry was performed on semithin sections to detect GLUT2 protein and sections were then stained with toluidine blue to detect GP granules. It was determined that GP astrocytes are frequently immunoreactive for the GLUT2 transporter protein. These data support the possibility that GP astrocytes may have an important influence upon the reactivity of the hypothalamus to glucose and that a specialized glucose metabolism may in part underlie the development of mitochondrial abnormalities in hypothalamic GP astrocytes.

Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

“…Glial cells are involved in glucose transport both into and within the brain and differentially express glucose transporters compared with neurons (25,27,28,(34)(35)(36). The mean levels of GLUT-1, expressed mainly in astrocyte endfeet surrounding blood vessels, and GLUT-2, expressed in astrocytes and tanycytes, were increased in the hypothalamus of NeoON rats ( Figure 3A; P < 0.0001 and Figure 3B; P < 0.05, respectively).…”

“…Not only is it an energy source, but central glucose levels also modulate systemic metabolism through a mechanism involving GLUT-2, expressed in hypothalamic astrocytes, ependymal-glial cells, tanycytes, and glucose-sensitive neurons (27)(28)(29)(30). Expression of this transporter in astrocytes is fundamental for central glucose sensing and regulation of food intake (30)(31)(32)(33).…”

Nervous glucose sensing regulates postnatal β cell proliferation and glucose homeostasis

“…In the central nervous system, immunohistochemical studies found GLUT2 expression in relatively rare neurons and astrocytes dispersed in many structures, including the hypothalamus, the brain stem, and the thalamic area (32)(33)(34)(35), as well as in tanycytes (36) and some endothelial cells (32). Because the low level of expression of GLUT2 in the brain makes its detection by standard immunocytochemical techniques difficult, we generated mice expressing a fluorescent reporter gene (eYFP) under the control of the GLUT2 promoter (37).…”

Hypothalamic Glucose-sensing: Role of Glia-to-Neuron Signaling

“…Besides "classical" stellate astrocytes distributed throughout the brain parenchyma, that express the glial fi brillary acidic protein (GFAP) for most of them, a particular cell-type, Gomori-positive astrocytes, is found in the AN of the hypothalamus [ 7 ] . Gomori-positive cells are characterized by numerous cytosolic granules derived from degenerating mitochondria [ 7 ] . Another population of glial-like cells, the tanycytes, are vimentine-positive cells lining the fl oor and the infra-lateral walls of the third ventricle.…”

“…In fact, in the AN, GLUT2 is associated with glial cells [ 31 ] . GLUT2 immunoreactivity is detected in astrocytes, which are, for most of them, also Gomoripositive [ 7 ] . In addition, in situ hybridization and immunohistochemical signals for both GK and GLUT2 were found to be associated with tanycytes bordering the third ventricle [ 32 , 33 ] .…”