Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain

Sotaro Momosaki, Miwa Ito, Misato Tonomura, Kohji Abe

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Glutamine synthetase (GS) plays an important role in glutamate neurotransmission or neurological disorder in the brain. [13N]Ammonia blood flow tracer has been reported to be metabolically trapped in the brain via the glutamate-glutamine pathway. The present study investigated the effect of an inhibitor of GS on [13N]ammonia uptake in order to clarify the feasibility of measuring GS activity in the living brain. l-Methionine sulfoximine (MSO), a selective GS inhibitor was microinjected into the ipsilateral striatum in rats. [13N]Ammonia uptake was quantified by autoradiography method as well as small animal positron emission tomography (PET) scans. The GS activity of the brain homogenate was assayed from the γ-glutamyl transferase reaction. Autoradiograms showed a decrease of [13N]ammonia radioactivity on the MSO-injected side compared with the saline-injected side of the striatum. This reduction could be detected with a small animal PET scanner. MSO had no effect on cerebral blood flow measured by uptake of [15O]H2O. The reduction of [13N]ammonia uptake was closely related to the results of GS activity assay. These results indicated that [13N]ammonia may enable measurement of GS activity in the living brain. Synapse 69:26-32, 2015.

Original languageEnglish
Pages (from-to)26-32
Number of pages7
JournalSynapse
Volume69
Issue number1
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

Keywords

  • Ammonia
  • Glutamine synthetase
  • In vivo
  • Positron emission tomography

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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