Species heterogeneity between gerbils and rats

Quinolinate production by microgila and astrocytes and accumulations in response to ischemic brain injury and systemic immune activation

Melvyn P. Heyes, Kuniaki Saito, Cai Y. Chen, Margit G. Proescholdt, Thaddeus S. Nowak, Ju Li, Karen E. Beagles, Martin A. Proescholdt, Mark A. Zito, Kensuke Kawai, Sanford P. Markey

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Quinolinic acid is an excitotoxic kynurenine pathway metabolite, the concentration of which increases in human brain during immune activation. The present study compared quinolinate responses to systemic and brain immune activation in gerbils and rats. Global cerebral ischemia in gerbils, but not rats; increased hippocampus indoleamine-2,3-dioxygenase activity and quinolinate levels 4 days postinjury. In a rat focal ischemia model, small increases in quinolinate concentrations occurred in infarcted regions on days 1,3, and 7, although concentrations remained below serum values. In gerbils, systemic immune activation by an intraperitoneal injection of endotoxin (1 mg/kg of body weight)increased quinolinate levels in brain, blood, lung, liver, and spleen, with proportional increases in lung indoleamine-2,3- dioxygenase activity at 24 h postinjection. In rats, however, no significant quinolinate content changes occurred, whereas lung indoleamine-2,3- dioxygenase activity increased slightly. Gerbil, but not rat, brain microglia and peritoneal monocytes produced large quantities of [13C6]quinolinate from L-[13C6]tryptophan. Gerbil astrocytes produced relatively small quantities of quinolinate, whereas rat astrocytes produced no detectable amounts. These results demonstrate that the limited capacity of rats to replicate elevations in brain and blood quinolinic acid levels in response to immune activation is attributable to blunted increases in local indoleamine- 2,3-dioxygenase activity and a low capacity of microglia, astrocytes, and macrophages to convert L-tryptophan to quinolinate.

Original languageEnglish
Pages (from-to)1519-1529
Number of pages11
JournalJournal of Neurochemistry
Volume69
Issue number4
Publication statusPublished - 01-10-1997

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Quinolinic Acid
Gerbillinae
Astrocytes
Brain Injuries
Rats
Brain
Chemical activation
Indoleamine-Pyrrole 2,3,-Dioxygenase
Microglia
Tryptophan
Lung
Blood
Kynurenine
Macrophages
Metabolites
Intraperitoneal Injections
Brain Ischemia
Endotoxins
Liver
Monocytes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Heyes, Melvyn P. ; Saito, Kuniaki ; Chen, Cai Y. ; Proescholdt, Margit G. ; Nowak, Thaddeus S. ; Li, Ju ; Beagles, Karen E. ; Proescholdt, Martin A. ; Zito, Mark A. ; Kawai, Kensuke ; Markey, Sanford P. / Species heterogeneity between gerbils and rats : Quinolinate production by microgila and astrocytes and accumulations in response to ischemic brain injury and systemic immune activation. In: Journal of Neurochemistry. 1997 ; Vol. 69, No. 4. pp. 1519-1529.
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abstract = "Quinolinic acid is an excitotoxic kynurenine pathway metabolite, the concentration of which increases in human brain during immune activation. The present study compared quinolinate responses to systemic and brain immune activation in gerbils and rats. Global cerebral ischemia in gerbils, but not rats; increased hippocampus indoleamine-2,3-dioxygenase activity and quinolinate levels 4 days postinjury. In a rat focal ischemia model, small increases in quinolinate concentrations occurred in infarcted regions on days 1,3, and 7, although concentrations remained below serum values. In gerbils, systemic immune activation by an intraperitoneal injection of endotoxin (1 mg/kg of body weight)increased quinolinate levels in brain, blood, lung, liver, and spleen, with proportional increases in lung indoleamine-2,3- dioxygenase activity at 24 h postinjection. In rats, however, no significant quinolinate content changes occurred, whereas lung indoleamine-2,3- dioxygenase activity increased slightly. Gerbil, but not rat, brain microglia and peritoneal monocytes produced large quantities of [13C6]quinolinate from L-[13C6]tryptophan. Gerbil astrocytes produced relatively small quantities of quinolinate, whereas rat astrocytes produced no detectable amounts. These results demonstrate that the limited capacity of rats to replicate elevations in brain and blood quinolinic acid levels in response to immune activation is attributable to blunted increases in local indoleamine- 2,3-dioxygenase activity and a low capacity of microglia, astrocytes, and macrophages to convert L-tryptophan to quinolinate.",
author = "Heyes, {Melvyn P.} and Kuniaki Saito and Chen, {Cai Y.} and Proescholdt, {Margit G.} and Nowak, {Thaddeus S.} and Ju Li and Beagles, {Karen E.} and Proescholdt, {Martin A.} and Zito, {Mark A.} and Kensuke Kawai and Markey, {Sanford P.}",
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Heyes, MP, Saito, K, Chen, CY, Proescholdt, MG, Nowak, TS, Li, J, Beagles, KE, Proescholdt, MA, Zito, MA, Kawai, K & Markey, SP 1997, 'Species heterogeneity between gerbils and rats: Quinolinate production by microgila and astrocytes and accumulations in response to ischemic brain injury and systemic immune activation', Journal of Neurochemistry, vol. 69, no. 4, pp. 1519-1529.

Species heterogeneity between gerbils and rats : Quinolinate production by microgila and astrocytes and accumulations in response to ischemic brain injury and systemic immune activation. / Heyes, Melvyn P.; Saito, Kuniaki; Chen, Cai Y.; Proescholdt, Margit G.; Nowak, Thaddeus S.; Li, Ju; Beagles, Karen E.; Proescholdt, Martin A.; Zito, Mark A.; Kawai, Kensuke; Markey, Sanford P.

In: Journal of Neurochemistry, Vol. 69, No. 4, 01.10.1997, p. 1519-1529.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Species heterogeneity between gerbils and rats

T2 - Quinolinate production by microgila and astrocytes and accumulations in response to ischemic brain injury and systemic immune activation

AU - Heyes, Melvyn P.

AU - Saito, Kuniaki

AU - Chen, Cai Y.

AU - Proescholdt, Margit G.

AU - Nowak, Thaddeus S.

AU - Li, Ju

AU - Beagles, Karen E.

AU - Proescholdt, Martin A.

AU - Zito, Mark A.

AU - Kawai, Kensuke

AU - Markey, Sanford P.

PY - 1997/10/1

Y1 - 1997/10/1

N2 - Quinolinic acid is an excitotoxic kynurenine pathway metabolite, the concentration of which increases in human brain during immune activation. The present study compared quinolinate responses to systemic and brain immune activation in gerbils and rats. Global cerebral ischemia in gerbils, but not rats; increased hippocampus indoleamine-2,3-dioxygenase activity and quinolinate levels 4 days postinjury. In a rat focal ischemia model, small increases in quinolinate concentrations occurred in infarcted regions on days 1,3, and 7, although concentrations remained below serum values. In gerbils, systemic immune activation by an intraperitoneal injection of endotoxin (1 mg/kg of body weight)increased quinolinate levels in brain, blood, lung, liver, and spleen, with proportional increases in lung indoleamine-2,3- dioxygenase activity at 24 h postinjection. In rats, however, no significant quinolinate content changes occurred, whereas lung indoleamine-2,3- dioxygenase activity increased slightly. Gerbil, but not rat, brain microglia and peritoneal monocytes produced large quantities of [13C6]quinolinate from L-[13C6]tryptophan. Gerbil astrocytes produced relatively small quantities of quinolinate, whereas rat astrocytes produced no detectable amounts. These results demonstrate that the limited capacity of rats to replicate elevations in brain and blood quinolinic acid levels in response to immune activation is attributable to blunted increases in local indoleamine- 2,3-dioxygenase activity and a low capacity of microglia, astrocytes, and macrophages to convert L-tryptophan to quinolinate.

AB - Quinolinic acid is an excitotoxic kynurenine pathway metabolite, the concentration of which increases in human brain during immune activation. The present study compared quinolinate responses to systemic and brain immune activation in gerbils and rats. Global cerebral ischemia in gerbils, but not rats; increased hippocampus indoleamine-2,3-dioxygenase activity and quinolinate levels 4 days postinjury. In a rat focal ischemia model, small increases in quinolinate concentrations occurred in infarcted regions on days 1,3, and 7, although concentrations remained below serum values. In gerbils, systemic immune activation by an intraperitoneal injection of endotoxin (1 mg/kg of body weight)increased quinolinate levels in brain, blood, lung, liver, and spleen, with proportional increases in lung indoleamine-2,3- dioxygenase activity at 24 h postinjection. In rats, however, no significant quinolinate content changes occurred, whereas lung indoleamine-2,3- dioxygenase activity increased slightly. Gerbil, but not rat, brain microglia and peritoneal monocytes produced large quantities of [13C6]quinolinate from L-[13C6]tryptophan. Gerbil astrocytes produced relatively small quantities of quinolinate, whereas rat astrocytes produced no detectable amounts. These results demonstrate that the limited capacity of rats to replicate elevations in brain and blood quinolinic acid levels in response to immune activation is attributable to blunted increases in local indoleamine- 2,3-dioxygenase activity and a low capacity of microglia, astrocytes, and macrophages to convert L-tryptophan to quinolinate.

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