Hyposmolality differentially and spatiotemporally modulates levels of glutamine synthetase and serine racemase in rat supraoptic nucleus

Abstract

Prolonged hyposmotic challenge (HOC) has a dual effect on vasopressin (VP) secretion [Yagil and Sladek (1990) Am J Physiol 258(2 Pt 2):R492-R500]. We describe an electrophysiological correlate of this phenomenon, whereby in vitro HOC transiently reduced the firing activity of VP neurons within the supraoptic nucleus of brain slices, which was followed by a rebound increase of their activity; this was paralleled by changes in the level of proteins relevant to astroglia-neuronal interactions. Hence, in vitro HOC transiently (at 5 min) increased the level of astrocyte-specific glial fibrillary acidic protein (GFAP), which then declined to control or base level (at 20 min); this was blocked by the gliotoxin L-aminoadipic acid, but not by tetanus toxin, which was used to inhibit neurotransmission. Similarly, in vivo HOC led to changes in GFAP level, which after an early increase (10 min) returned to normal (30 min). Immunoassays revealed that neuronal, but not astrocytic, expression of serine racemase (SR) was increased at the late stage of HOC in vivo, whereas at an early stage there was a transient increase in level of the astrocyte-specific glutamine synthetase (GS). Furthermore, there was an increased molecular association between GFAP and GS at 10 min, whereas SR increased its association with the neuronal nuclear antigen NeuN at 30 min. These results suggest that the dual effect of HOC on VP neuronal secretion/activity could be related to metabolic/signaling changes in astrocytes (glutamate-glutamine conversion) and neurons (D-serine synthesis/ammonia production), which may account for the rebound in VP neuronal activity, presumably by promoting the activation of neuronal glutamate receptors.

Chemically functionalized single-walled carbon nanotubes enhance the glutamate uptake characteristics of mouse cortical astrocytes

“…Since, the loss of astrocyte-specific intermediate filaments, GFAP and vimentin, have hampered vesicular trafficking (Potokar et al 2007) and the loss of GFAP in particular led to a reduced trafficking of glutamate transporters to the surface of astrocytes (Hughes et al 2004), it is plausible that an increase in GFAP-ir due to SWCNT-PEG leads to an increase in the trafficking of glutamate transporters to the plasma membrane, which can in turn increase the uptake of glutamate. In addition to this, an increase in GFAP levels is correlated with an increase in the levels of glutamine synthetase (Wang and Hatton 2009; Wang et al 2013), an enzyme that converts glutamate to glutamine in astrocytes, and an increased glutamine synthetase expression leads to an increase in glutamate uptake and glutamine release (Zou et al 2010). Unlike glutamate, glutamine released into the extracellular space does not stimulate the receptors present on the neurons, pointing to an additional possible mechanism by which CNTs may mediate beneficial effects in neuroprosthesis applications, e.g., injury, with glutamate-mediated excitotoxicity settings in place.…”

The Rise and Fall of the d -Serine-Mediated Gliotransmission Hypothesis

“…No immunoreactivity was observed in Bergmann glia cells, confirming a predominant neuronal expression. Moreover, astrocytic SR was either not detectable [28] or found predominantly in the magnocellular neurons of the rat supra-optic nucleus [29], where glia-derived D-serine had been incorrectly assumed to control synaptic plasticity [6]. …”

Interactions of the Mechanosensitive Channels with Extracellular Matrix, Integrins, and Cytoskeletal Network in Osmosensation

“…Consistently, in acute hyponatremic condition, serum VP levels increase significantly following initial inhibition (Yagil and Sladek, 1990), which reflects a reactivation of VP neurons following the initial inhibition (Wang et al, 2013a,b) through the mechanism of “resetting osmosensory threshold at the local neural circuit” (Wang et al, 2011). Clearly, the activation of these TRPV channels could occur under both hyperosmotic and hyposmotic challenges.…”

“…Thus, an increased interactions between microtubule network with TRPV1 during cell shrinkage could account for hyperosmotic activation of osmosensory neurons (Prager-Khoutorsky and Bourque, 2015). However, this hypothesis could not explain hyposmotic intracellular Ca 2+ increase (Aure et al, 2010; Soya et al, 2014; Jo et al, 2016), the recovery of VP neuronal activity from hyposmotic inhibition (Wang et al, 2013a,b) and the increased VP secretion during volemic increase in chronic osmotic stress (Zhang et al, 2001). Here, referring to the hearing mechanism (Sukharev and Corey, 2004; Martinac, 2014), we propose that if hyperosmotic activation of TRP channels is due to a “push” of microtubule network (Prager-Khoutorsky and Bourque, 2015), the hyposmotic activation of TRP channels should be because of a “pull” of the network in coordination with conformational changes in other cellular components (Figure 1A).…”

“…Importantly, astrocytes can influence neuronal activity through multiple approaches (Wang and Zhu, 2014; Hertz and Chen, 2016; Wang and Parpura, 2016). For instance, β-alanine release from astrocytes (Pasantes-Morales et al, 1994) can inhibit astrocyte GABA transporters and thus inhibits VP secretion through increasing extracellular GABA (Wang et al, 2013a); coordinated D-serine metabolism between astrocytes and magnocellular neurons along with exhaustion of β-alanine and taurine in the SON can increase NMDA receptor activation, and participate in the recovery of VP neurons from hyposmotic inhibition (Wang et al, 2013b). Thus, astrocytes are important osmosensory cells not only by co-expression of TRPV channels and AQP4 (Benfenati et al, 2011; Mola et al, 2016; Iuso and Križaj, 2016) but also by astrocytic plasticity-associated neuronal effects (Hou et al, 2016; Jia et al, 2016).…”