Direct hypertonic stimulation of the rat supraoptic nucleus increases c-fos expressionin glial cells rather than magnocellular neurones

Abstract

We investigated whether hypertonicity acts directly on supraoptic neurones to activate c-fos expression. Hypertonic artificial cerebrospinal fluid was infused into the supraoptic nucleus (SON) via a microdialysis probe implanted 24 h previously. The rats were decapitated after 90 min for immunohistochemistry with a Fos protein antibody. Direct hypertonic stimulation increased Fos protein expression in glial cells, identified by glial fibrillary acidic protein immunoreactivity, but not in magnocellular neurones. Similarly, with in situ hybridisation c-fos mRNA expression was predominantly seen in glial cells. Fos expression in SON neurones was stimulated by systemic hypertonicity even with a microdialysis probe in the SON, and magnocellular neurones expressed Fos after direct microinjection of cholecystokinin-8S into the SON. Thus, while direct hypertonic stimulation of SON neurones activates secretion of vasopressin and oxytocin, the c-fos gene is not activated, unlike following systemic hypertonic stimulation. This indicates that excitation of neuronal electrical and secretory activity does not necessarily lead to activation of the c-fos gene. Activation of c-fos expression in glial cells by direct hypertonic stimulation may reflect their role in regulating brain extracellular fluid composition.

Effects of vagotomy, splanchnic nerve lesion, and fluorocitrate on the transmission of acute hyperosmotic stress signals to the supraoptic nucleus

“…Previous studies by our group and others have revealed that acute hypertonic stimuli lead to the up-regulation of GFAP in SON astrocytes (Lafarga et al, 1992;Yuan et al, 2010), and SON astrocyte activation correlates with the up-regulation of Fos in SON neurons (Ludwig et al, 1997;Yuan et al, 2010). In the present study, we found that Fos and GFAP expression in SON and SON-VGL astrocytes was significantly increased by treatment with HS.…”

“…Furthermore, the release of taurine by astrocytes in the SON in response to hypotonic stimuli activates neuronal glycine receptors and inhibits the release of VP (Deleuze et al, 1998;Hussy et al, 2001). Moreover, Fos expression is enhanced in SON glial cells in response to direct hypertonic stimulation, similarly to SON neurons (Fenelon et al, 1994;Ludwig et al, 1997;Miyata et al, 2001;Yuan et al, 2010). The dynamic interrelationship between astrocytic plasticity and neuronal activity in the SON is also essential for other physiological processes regulated by the SON, such as the milk-ejection reflex, stress, and the whole-body fluid balance control (Hatton, 2002;Wang and Hatton, 2009).…”

Involvement of non-neuronal brain cells in AVP-mediated regulation of water space at the cellular, organ, and whole-body level

“…This possibility is suggested by extensive astrocytic but not neuronal localization of the water channel, aquaporin-4, in the SON (Nielsen et al, 1997). It is further supported by the observations that osmotic stimulation causes morphological changes in SON astrocytes in vivo (Lafarga et al 1992), and that microperfusion of the SON with hypertonic solution selectively increases the expression of c-fos in astrocytes (Ludwig et al, 1997). During exposure to hypertonic plasma in the early phase of hypernatremia, i.e., before a complete compensatory increase has occurred of brain electrolytes, water might possibly be drawn from astrocytic endfeet surrounding the capillary.…”

High Salt Culture Conditions Inhibit Serum- and NGF- but not PMA-Induced Egr-1 Gene Transcription in Rat C6 Glioma Cells

“…For example, the hyperosmotic media containing high concentrations of NaCl, sucrose, or urea have been shown to induce the expression of immediate early gene c-fos and egr-1 (also known as NGFI-A, zif268, in cardiomyocytes and kidney cells (Cohen 1996;Cohen et al 1994Cohen et al , 1991Wollnik et al 1993). On the other hand, the in vivo studies have shown that the intraperitoneal injection of hyperosmotic saline solution can increase the DNA binding activity of AP-1 in rat hypothalamic supraoptic and paraventricular nuclei (Ying et al 1996) and also shown that the direct infusion of hyperosmotic artificial cerebrospinal fluid into rat supraoptic nucleus increases both c-fos mRNA and protein levels in glial cells, suggesting that hyperosmotic stimulation may stimulate c-fos gene expression in this brain region (Ludwig et al 1997). Therefore, it seems possible that hyperosmotic stress may affect the metabolism and function as well as the proliferation and differentiation of neuronal and glial cells through the stimulation of immediate early gene expression.…”