Association between cell swelling and glycogen content in cultured astrocytes

Abstract

Treatment of cultured rat astrocytes with hypotonic media or with 1 mM glutamate for 90 min caused cell swelling and a significant increase in glycogen content. Conversely, treatment with hypertonic media caused cell shrinkage with a corresponding decrease in astrocyte glycogen, which was proportional to the increasing osmolality of the hypertonic media. The glutamate receptor antagonist, MK-801, lowered both the glutamate-induced swelling and glycogen increase. These findings demonstrate a correlation between changes in cell volume and astrocyte glycogen content. This may explain the increased astrocytic glycogen observed in many neuropathological conditions where astrocyte swelling occurs. Because glycogen represents the largest energy reserve in the central nervous system, a swelling-induced disturbance in glycogen metabolism may lead to abnormal glial-neuronal interactions resulting in impaired brain bioenergetics.

Hypoosmotic swelling increases protein tyrosine nitration in cultured rat astrocytes

“…On the one hand, glutamate induces astrocyte swelling, which was shown to be mediated by NMDA receptor activation, Ca 2ϩ influx, and formation of reactive oxygen/nitrogen intermediates, including NO Dombro et al, 2000). Likewise, ammonia-induced cell swelling depends on NMDA receptor activation, oxidative stress, and NO formation (Murthy et al, 2001;Zielinska et al, 2003).…”

“…Astrocyte swelling triggers volume regulatory osmolyte fluxes (O'Connor and Kimelberg, 1993) and stimulates glycogen synthesis (Dombro et al, 2000) and remodeling of the actin cytoskeleton (Moran et al, 1996). In addition, astrocyte swelling is suggested to be a signal for proliferation and thus play a role in gliosis (Reichenbach, 1989).…”

Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices

“…In contrast, reactive oxygen species (ROS) mediate astrocyte swelling as induced by glutamate (Bender et al, 1998;Dombro et al, 2000) or ammonia (Norenberg et al, 2005), respectively. In contrast, astrocyte swelling stimulates the production of ROS (Schliess et al, 2004) and astrocyte swelling may account for the increase of cerebral NO production in ammonia-loaded rats (Master et al, 1999).…”

Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice

“…The potential importance of the CNS glycogen stores has recently received increased attention. Glycogen provides a material basis for astrocyte function and energy for neuronal activity and survival (Dombro et al, 2000;Dienel and Cruz, 2004). Studies on cell cultures have shown that increased amounts of glycogen in astrocytes can extend the lifespan of neurons (Brown et al, 2005).…”