Abstract
Reports that food intake is stimulated by intracerebroventricular (icv) administration of the SGLT1 Na+-D-glucose cotransport inhibitor, phlorizin, suggest that decreased central glucose uptake is a stimulus for compensatory motor activity underlying restoration of energy imbalance. In order to identify central cell populations that are functionally responsive to decreased SGLT1 function in the brain, the present study utilized immunocytochemical techniques to demonstrate cellular expression of the inducible activator protein-1 transcription factor, Fos, following icv delivery of phlorizin. Groups of adult male rats were treated with phlorizin at a dose of 10, 50, or 250 μg/animal, then sacrificed 2hr later by transcardial perfusion. Ependymal expression of Fos-immunoreactivity (-ir) was observed throughout most of the cerebroventricular system, except the medullary fourth ventricle, at each dose examined. Higher doses of the transport inhibitor elicited immunostaining of periventricular glia, characterized by cytoplasmic glial fibrillary acidic protein-ir, underlying the lateral, third, and rostral fourth ventricles and cerebral aqueduct. These doses also resulted in the transcriptional activation of neurons in discrete brain sites, including the rostral medial preoptic area, median preoptic n., preoptic and hypothalamic periventricular n., subfornical organ, thalamic medial habenular and paraventricular n., hypothalamic paraventricular, ventromedial, and arcuate n., and n. of the solitary tract. These results show that nonexcitable cells located throughout much of the central neuroaxis and discrete populations of neurons in the brain are genomically responsive to pharmacological inhibition of central SGLT1 function. Evidence for the functional responsiveness of these cell types to manipulation of energy-dependent glucose transport suggests that cellular uptake of this metabolic fuel may serve as an indicator of central energy substrate availability, and that alterations in glucose uptake via this specific mechanism may be the source of regulatory signals involved in the maintenance of energy homeostasis.
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Briski, K.P., Marshall, E.S. Induction of Ependymal, Glial, and Neuronal Transactivation by Intraventricular Administration of the SGLT1 Na+-D-Glucose Cotransporter Inhibitor Phlorizin. Neurochem Res 26, 783–792 (2001). https://doi.org/10.1023/A:1011655901032
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DOI: https://doi.org/10.1023/A:1011655901032