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

Sotaro Momosaki, Miwa Ito, Misato Tonomura, Koji 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

Fingerprint

Glutamate-Ammonia Ligase
Ammonia
Methionine Sulfoximine
Brain
Positron-Emission Tomography
Glutamic Acid
Cerebrovascular Circulation
Transferases
Nervous System Diseases
Glutamine
Autoradiography
Synaptic Transmission
Synapses
Radioactivity

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain. / Momosaki, Sotaro; Ito, Miwa; Tonomura, Misato; Abe, Koji.

In: Synapse, Vol. 69, No. 1, 01.01.2015, p. 26-32.

Research output: Contribution to journalArticle

Momosaki, Sotaro ; Ito, Miwa ; Tonomura, Misato ; Abe, Koji. / Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain. In: Synapse. 2015 ; Vol. 69, No. 1. pp. 26-32.
@article{6c2d85d5c2494f2d980ac8265d631152,
title = "Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain",
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.",
keywords = "Ammonia, Glutamine synthetase, In vivo, Positron emission tomography",
author = "Sotaro Momosaki and Miwa Ito and Misato Tonomura and Koji Abe",
year = "2015",
month = "1",
day = "1",
doi = "10.1002/syn.21781",
language = "English",
volume = "69",
pages = "26--32",
journal = "Synapse",
issn = "0887-4476",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain

AU - Momosaki, Sotaro

AU - Ito, Miwa

AU - Tonomura, Misato

AU - Abe, Koji

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Ammonia

KW - Glutamine synthetase

KW - In vivo

KW - Positron emission tomography

UR - http://www.scopus.com/inward/record.url?scp=84910637655&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84910637655&partnerID=8YFLogxK

U2 - 10.1002/syn.21781

DO - 10.1002/syn.21781

M3 - Article

C2 - 25196365

AN - SCOPUS:84910637655

VL - 69

SP - 26

EP - 32

JO - Synapse

JF - Synapse

SN - 0887-4476

IS - 1

ER -