Region-selective glutamine synthetase expression in the rat central nervous system following portocaval anastomosis

Abstract

Glutamine synthetase (GS) content was investigated using immunohistochemical methods in the hippocampus, cerebellum and spinal cord of rats after long-term portocaval anastomosis (PCA). Six months after surgery, GS content was increased in several areas of each region and decreased in others, compared with controls. In the hippocampus, the CA1-CA3 pyramidal subfields and the dentate molecular layer had a high level of GS expression; PCA reduced GS content in other hippocampal regions, such as the dentate hilus. In the cerebellum, PCA significantly increased GS immunoreactivity in the Bergmann glial processes of the molecular layer and decreased GS immunoreactivity in astrocytes of the granule cell layer. In the spinal cord, GS immunoreactivity increased in the dorsal horn and decreased in the ventral horn. Blood vessels located in zones with GS-immunopositive perineuronal astrocytes in PCA-exposed brains were surrounded by strongly GS-immunostained perivascular processes. These results suggest that PCA exposure had a differential effect on GS expression in different regions of the central nervous system. The increased immunoreactivity of GS-positive cells in PCA-exposed brains correlates with glutamatergic areas, which may contribute to protecting neurons against extracellular glutamate and/or ammonia excess.

Rats with minimal hepatic encephalopathy due to portacaval shunt show differential increase of translocator protein (18 kDa) binding in different brain areas, which is not affected by chronic MAP-kinase p38 inhibition

“…There is a good number of studies on the effects of PCS on astrocytes, showing changes that are different in depending on the brain region (Bodega et al 1991; Suárez et al 1997) and on the time after PCS surgery (Ma et al 1991). In general these studies show enlarged nuclear size (Diemer and Laursen 1977), increased astrocyte cell and cytoplasmic area (Laursen and Diemer 1980) and no evidence of Alzheimer type II cells (Pilbeam et al 1983).…”

Astroglial Glutamate–Glutamine Shuttle Is Involved in Central Sensitization of Nociceptive Neurons in Rat Medullary Dorsal Horn

“…A key and specific process of astroglial function is the glutamateglutamine shuttle, which includes the uptake of the excess extrasynaptic glutamate and the production (via astroglial enzyme GS) and release from astroglia of glutamine, which is then taken up by neuronal elements to replenish the supply of glutamate (Zwingmann and Leibfritz, 2003;Hertz, 2004;Hertz and Zielke, 2004;Fonseca et al, 2005), which plays a major role in central sensitization (Dubner and Basbaum, 1994;Sessle, 2000;Woolf and Salter, 2006). In the spinal cord as well as the brain, GS exists in astroglia and oligodendrocytes but not in neurons (Norenberg, 1979;Warringa et al, 1988;Cammer, 1990;Suarez et al, 1997Suarez et al, , 2002; however, some earlier radio-assay studies reported that GS may also exist in cultured cortical neurons (Zwingmann and Leibfritz, 2003). Although there is a lack of direct evidence for altered astroglial GS activity in the spinal cord related to peripheral inflammatory events, recent studies have reported that GS activity is increased in the white and gray matters of lumbar as well as cervical enlargements 7 d after spinal cord injury in rats (Benton et al, 2000).…”

Effect of glutamine synthetase inhibition on astrocyte swelling and altered astroglial protein expression during hyperammonemia in rats

“…Others have found decreased GS activity and either no change or increased expression after prolonged portacaval anastomosis (Suarez et al, 1997(Suarez et al, , 2002Desjardins et al, 1999). We observed no changes in cortical GS activity or in the overall optical density of immunostained sections of cortex during 24 h of hyperammonemia.…”