Glutamine synthetase in brain: effect of ammonia

@article{Surez2002GlutamineSI,
  title={Glutamine synthetase in brain: effect of ammonia},
  author={Isabel Su{\'a}rez and Guillermo Bodega and Benjam{\'i}n Fern{\'a}ndez},
  journal={Neurochemistry International},
  year={2002},
  volume={41},
  pages={123-142}
}
Toxic effects of glutamine in the CNS are triggered by its accumulation in astrocytic mitochondria
TLDR
Evidence that many aspects of ammonia toxicity in HE-affected brain are mediated by glutamine (Gln), synthesized in excess from ammonia and glutamate by glutamines synthetase (GS), an astrocytic enzyme is discussed.
Glutamine Synthetase: Role in Neurological Disorders.
TLDR
This review summarizes changes in GS gene expression/activity and its potential contribution to the pathogenesis of several neurological disorders, including hepatic encephalopathy, ischemia, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's Disease, and astroglial neoplasms.
Glutamine as a mediator of ammonia neurotoxicity: A critical appraisal.
In vivo neuroprotective adaptation of the glutamate/glutamine cycle to neuronal death
TLDR
It is concluded that the graded modification of the glutamate‐glutamine correlation and neuronal lactate availability may be key factors in the apoptotic and necrotic neuronal demise, whose control may prove highly useful to potentiate neuronal survival.
Disturbance of the Glutamate-Glutamine Cycle, Secondary to Hepatic Damage, Compromises Memory Function
TLDR
Data indicates that learning and spatial memory, as well as discriminatory or other information acquisition processes in the CNS, are damaged by the appearance of hyperammonemia and, moreover, are associated with a reduction in the production of cyclic guanosine monophosphate (cGMP).
Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy
TLDR
Glial glutamine synthetase is downregulated in the hippocampal sclerosis (HS) hippocampus of temporal lobe epilepsy (TLE) patients in areas with severe neuron loss, and may be part of the mechanism underlying impaired glutamate clearance found in the hippocampus of TLE patients with HS.
Hyperammonemia compromises glutamate metabolism and reduces BDNF in the rat hippocampus
Ammonia-Induced Glial-Inflammaging
TLDR
The main findings pointed that ammonia increased the gene expression of proteins associated with BBB permeability, in addition to cause an inflammatory response and decrease the release of trophic factors, which were dependent on p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor κB (NFκB) pathways and aquaporin 4, in both neonatal and mature astrocytes.
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References

SHOWING 1-10 OF 267 REFERENCES
The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission
TLDR
It is proposed that an ammonia‐induced abnormality in astroglial glutamate uptake constitutes a critical aspect in the pathogenesis of hepatic encephalopathy and other hyperammonemic conditions.
Astrocytic pathology of methionine sulfoximine-induced encephalopathy
TLDR
The results indicate certain regionalizations in the roles of astrocytes and oligodendrocyte in glutamate and ammonia metabolisms.
Gliotoxicity in brain reaggregate cultures caused by oxidants and excitatory amino acids can be prevented by alpha-tocopherol and MK-801.
TLDR
It is demonstrated that inactivation of GS can be caused by free radical insult whereas stimulation of brain GS and reactive gliosis is produced by excitatory amino acids acting at neuronal NMDA receptors.
Excitatory Amino Acids and Hepatic Encephalopathy
TLDR
Results suggest that extracellular glutamate (or aspartate) may be increased in sustained hyperammonemia, probably as a result of loss of astrocytic integrity in hepatic encephalopathy.
Glutamine synthetase modulation in astrocyte cultures of different mouse brain areas
Astroglial cells from mouse cerebral hemispheres, cerebellum, olfactory bulbs, and medulla oblongata were grown in the presence of either hormones (hydrocortisone, insulin) or cell second messengers
Evidence for an Astrocytic Glutamate Transporter Deficit in Hepatic Encephalopathy
TLDR
Ammonia-induced reductions in expression of GLT-1 resulting in increased extracellular glutamate concentrations could explain some of the symptoms (hyperexcitability, cerebral edema) characteristic of hepatic encephalopathy in acute liver failure.
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