In situ localization and osmotic regulation of the Na⁺myo-inositol cotransporter in rat brain

Organic osmolytes accumu-late in the mammalian brain when plasma osmolality is elevated chronically. An understanding of organic osmolyte regulation is important for elucidating the pathophysiology of numerous disease states, particularly those in which plasma osmolality is altered or manipulated. To this end, we have previously characterized the mechanisms of osmoregulatory myo-inositol accumulation and loss in rat brain glial cells. The validity of cell culture models of physiological functions, however, requires demonstration of similar behavior in vivo. We therefore examined the effect of serum hypertonicity and its correction on expression of the Na⁺-myo-inositol cotransporter (SMIT) in rat brain. Northern analysis revealed that chronic serum hypertonicity increased brain SMIT mRNA levels four- to sevenfold. Rapid reduction of serum osmolality caused a rapid fall in SMIT mRNA levels. In situ hybridization revealed a widespread distribution of cells expressing SMIT with striking regional variability in the number of and intensity of cells labeled. These results confirm and extend our studies of cultured glial cells and indicate that myo-inositol accumulation in vivo is due to increased expression of SMIT. Regional variability in the distribution of SMIT may be a factor in the differential vulnerability of certain brain regions to shifts in plasma osmolality.