Differential response of glutamine in cultured neurons and astrocytes

K. V. Rama Rao, A. R. Jayakumar, Micheal D. Norenberg

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Glutamine, a byproduct of ammonia detoxification, is found elevated in brain in hepatic encephalopathy (HE) and other hyperammonemic disorders. Such elevation has been implicated in some of the deleterious effects of ammonia on the central nervous system (CNS). Recent studies have shown that glutamine results in the induction of the mitochondrial permeability transition (MPT) in cultured astrocytes. We examined whether glutamine shows similar effects in cultured neurons. Both cultured astrocytes and neurons were exposed to glutamine (6.5 mM) for 24 hr and the MPT was assessed by changes in cyclosporin A (CsA)-sensitive inner mitochondrial membrane potential (ΔΨ m) using the potentiometric dye tetramethylrhodamine ethyl ester (TMRE). Glutamine significantly dissipated the (ΔΨm) in astrocytes as demonstrated by a decrease in mitochondrial TMRE fluorescence, a process that was blocked by CsA. On the other hand, treatment of cultured neurons with glutamine had no effect on the (ΔΨm). Dissipation of the (ΔΨm) in astrocytes by glutamine was blocked by treatment with 6-diazo-5-oxo-L-norleucine (DON; 100 μM), suggesting that glutamine hydrolysis and the subsequent generation of ammonia, which has been shown previously to induce the MPT, might be involved in MPT induction by glutamine. These data indicate that astrocytes but not neurons are vulnerable to the toxic effects of glutamine. The selective induction of oxidative stress and the MPT by glutamine in astrocytes may partially explain the deleterious affects of glutamine on the CNS in the setting of hyperammonemia, as well as account for the predominant involvement of astrocytes in the pathogenesis of HE and other hyperammonemic conditions.

Original languageEnglish (US)
Pages (from-to)193-199
Number of pages7
JournalJournal of Neuroscience Research
Issue number1-2
StatePublished - Jan 15 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience


  • Ammonia toxicity
  • Astrocytes
  • Cyclosporin A
  • Glutaminase
  • Glutamine
  • Hepatic encephalopathy
  • Mitochondrial permeability transition
  • Neurons
  • Oxidative stress


Dive into the research topics of 'Differential response of glutamine in cultured neurons and astrocytes'. Together they form a unique fingerprint.

Cite this