The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission

Norenberg, Michael D.; Huo, Zhifeng; Neary, Joseph T.; Roig‐Cantesano, Ana

doi:10.1002/(sici)1098-1136(199709)21:1<124::aid-glia14>3.3.co;2-t

Cited by 9 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This could be an alternative explanation for the observed correlation between GLT and APP expression (Li et al, 1997) and would be in agreement with the reports on reduced density of glutamate receptors in AD (e.g., Greenamyre et al, 1985;Chalmers et al, 1990;Dewar et al, 1991;Scheuer et al, 1996). In addition to amyotrophic lateral sclerosis Lin et al, 1998), low GLT levels have been found in liver coma (Knecht et al, 1997;Norenberg et al, 1997). The control sample in our material with the lowest GLT level (but the highest level of GLAST) is case #2 (Fig.…”

Section: Pathological Significance Of Reduction In Glutamate Uptakesupporting

confidence: 91%

Interindividual differences in the levels of the glutamate transporters GLAST and GLT, but no clear correlation with Alzheimer's disease

et al. 1999

View full text Add to dashboard Cite

Alzheimer's disease is a common progressive neurodegenerative disease of unknown etiology. Several different pathological processes have been identified in the brains of Alzheimer patients. To determine if reduced glutamate uptake is a contributing factor, we have measured the levels of the glutamate transporter proteins GLAST (EAAT1) and GLT (EAAT2) in human autopsy samples. The postmortem proteolysis of these proteins turned out to be fairly rapid. Brains from 10 Alzheimer and 10 control patients were therefore obtained with a relatively short postmortem delay (5 hr on average). GLT (N-terminal and central parts), GLAST (C-terminal), glial fibrillary acidic protein (GFAP) and inositol (1,4,5)-triphosphate (IP3)-receptor immunoreactivities were determined in the cingulate and inferior temporal gyri by immunoblotting. The Na+-dependent "binding" of D-[3H]aspartate and the glutamate uptake after solubilization and reconstitution in liposomes were determined for comparison. An individual variation in GLAST and GLT levels was found, but no significant correlation with Alzheimer's disease, except for a 14% lower ratio of N-terminal to central GLT immunoreactivity (P < 0.04). The levels of GLAST and GLT showed negative correlation in agreement with the idea that these proteins are differentially regulated. In conclusion, Alzheimer's disease brains can have both normal and reduced levels of GLAST and GLT.

show abstract

Section: Pathological Significance Of Reduction In Glutamate Uptakesupporting

confidence: 91%

Interindividual differences in the levels of the glutamate transporters GLAST and GLT, but no clear correlation with Alzheimer's disease

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Knecht and co-workers (1997) showed significant down-regulation of EAAT-2 protein and mRNA in frontal cortex of ALF comatose rats compared to sham operated controls (Knecht et al 1997). A significant decrease of EAAT-2 mRNA levels was demonstrated in brain tissues from rats with thioacetamide (TAA)-induced ALF and of hyperammonemic rats by northern blot analyses (Norenberg et al 1997). Prolonged treatment of cultured rat astrocytes with ammonia has been shown to induce an increase in extracellular glutamate (Ohara et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Expression of astrocytic genes coding for proteins implicated in neural excitation and brain edema is altered after acute liver failure

Thumburu

Dhiman

Vasishta

et al. 2013

Journal of Neurochemistry

View full text Add to dashboard Cite

In vitro and in vivo studies have suggested that reduced astrocytic uptake of neuronally released glutamate, alterations in expression of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP-4) contribute to brain edema in acute liver failure (ALF). However, there is no evidence to date to suggest that these alterations occur in patients with ALF. We analyzed the mRNA expression of excitatory amino acid transporters (EAAT-1, EAAT-2), GFAP, and AQP-4 in the cerebral cortex obtained at autopsy from eight patients with ALF and from seven patients with no evidence of hepatic or neurological disorders by real-time PCR, and protein expression was assessed using immunoblotting and immunohistochemistry. We demonstrated a significant decrease in GFAP mRNA and protein levels in ALF patients compared to controls. While the loss of EAAT-2 protein in ALF samples was post-translational in nature, EAAT-1 protein remained within normal limits. Immunohistochemistry confirmed that, in all cases, the losses of EAAT-2 and GFAP were uniquely astrocytic in their localization. AQP-4 mRNA expression was significantly increased and its immunohistochemistry demonstrated increased AQP-4 immunoreactivity in the glial end-feet process surrounding the microvessels. These findings provide evidence of selective alterations in the expression of genes coding for key astrocytic proteins implicated in central nervous system (CNS) excitability and brain edema in human ALF. Keywords: acute liver failure, aquaporin-4, astrocyte protein, brain edema, EAAT-1, EAAT-2, GFAP.

show abstract

“…Hepatic encephalopathy (HE) is a complex neurological disorder associated with acute or chronic liver failure in which ammonia is a major neurotoxin (Norenberg, 1996;Butterworth, 1997;Albrecht, 1998). Repeated (2-3 times) administration to rats or mice of a hepatotoxin, thioacetamide (TAA), at 24-hr intervals is a routine procedure to induce neurophysiological symptoms and changes in blood and brain biochemistry and brain morphology characteristic of acute HE (Trennery and Waring, 1983;Albrecht and Hilgier, 1984;Albrecht et al, 1988;Zimmermann et al, 1989;Peeling et al, 1993, Hilgier andOlson, 1994;Norenberg et al, 1997). However, the course of HE after cessation of the treatment has not been studied in detail.…”

Section: Introductionmentioning

confidence: 99%

Changes in the extracellular profiles of neuroactive amino acids in the rat striatum at the asymptomatic stage of hepatic failure

et al. 1999

View full text Add to dashboard Cite

Rats were treated with a hepatotoxin thioacetamide (TAA) and examined 21 days later, when they showed moderate fatty metamorphosis of the liver and morphological changes in brain indicative of excitotoxic neuronal damage, but no evident biochemical or neurophysiological symptoms of hepatic encephalopathy (HE). High-performance liquid chromatography (HPLC) analysis of extracellular amino acids in striatal microdialysates of TAA-treated rats revealed a significant increase in the excitatory amino acids glutamate (Glu) and aspartate (Asp) and their amino acid metabolites glutamine (Gln) and alanine (Ala). Microdialysis in the presence of 50 mM K+ triggered in TAA-treated rats an accumulation of Asp and Glu, and diminished the accumulation of Gln. These effects were virtually absent in control rats. None of the treatments affected the accumulation of the nontransmitter amino acid leucine (Leu). The above changes mirror those previously described in symptomatic HE and are likely to contribute to excitotoxic damage. The basal microdialysate content of taurine (Tau), an amino acid with antioxidant and volume regulatory properties, was 60% lower in TAA-treated rats than in control rats despite its increased blood-to-brain transport. The decrease in extracellular Tau may thus reflect Tau redistribution to adjacent central nervous system (CNS) cells manifesting a cell-protective response. Stimulation with 50 mM K+ increased extracellular Tau in control rats by 182% and in TAA-treated rats by 322%. Stimulation with 100 microM N-methyl-D-aspartate (NMDA) increased extracellular Tau in control rats by 27 % and in TAA-treated rats by as much as 250%. The increase of K+- or NMDA-dependent Tau release may reflect improved cell volume regulation and neuroprotection and contribute to attenuation of neurologic symptoms in rats with liver failure.

show abstract

The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission

Cited by 9 publications

References 0 publications

Interindividual differences in the levels of the glutamate transporters GLAST and GLT, but no clear correlation with Alzheimer's disease

Interindividual differences in the levels of the glutamate transporters GLAST and GLT, but no clear correlation with Alzheimer's disease

Expression of astrocytic genes coding for proteins implicated in neural excitation and brain edema is altered after acute liver failure

Changes in the extracellular profiles of neuroactive amino acids in the rat striatum at the asymptomatic stage of hepatic failure

Contact Info

Product

Resources

About