Cerebral metabolic effects of organophosphorus anticholinesterase compounds

Alexander L Miller, Miguel A. Medina

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Rats treated intravenously with an organophosphoras anticholinesterase compound, paraoxon or soman, were sacrificed 2 to 131 min later, using 0.7sec of focused microwave irradiation (25 kW at 915 MHz). Brain regional rates of glucose utilization during 3-min intervals were determined with labeled glucose and fluorodeoxyglucase as tracers. Levels of glucose, lactate, ATP, and creatine phosphate were assayed in the same samples. The two compounds differed markedly in their effects on brain metabolism. Paraoxon (0.8LD50) depressed rates of glucose use in all brain regions, without causing consistent changes in brain metabolite levels. This depressant effect was most pronounced during the first 30 min after toxin exposure and had largely disappeared by 2hr. Soman (0.8-0.95 LD50) was variable in its effects. Animals that showed seizure-like behavior had marked increases in glucose use in diencephalon and cerebrum but no changes in cerebellum or brain stem. Rapid rates of glucose use were associated with high levels of lactic acid and lower levels of creatine phosphate. In cerebrum, but not diencephalon, levels of ATP fell by as much as 50% in strongly affected animals by 30-130 min after soman. All of these effects were reversible with atropine. Soman-treated animals that did not have seizure-like activity did not exhibit these brain metabolic changes. These results and those of others show that cholinergic compounds vary greatly in their effects on brain glucose and energy metabolism. Although noncholinergic mechanisms are a possibility, the most parsimonious explanation for these findings is that cholinesterase inhibitors vary in their affinity for different central nervous system (CNS) acetylcholine receptor populations.

Original languageEnglish (US)
Pages (from-to)147-156
Number of pages10
JournalMetabolic Brain Disease
Volume1
Issue number2
DOIs
StatePublished - Jun 1986

Fingerprint

Organophosphorus Compounds
Cholinesterase Inhibitors
Brain
Soman
Glucose
Paraoxon
Diencephalon
Animals
Phosphocreatine
Cerebrum
Lactic Acid
Seizures
Adenosine Triphosphate
Microwave irradiation
Lethal Dose 50
Neurology
Cholinergic Receptors
Metabolites
Microwaves
Atropine

Keywords

  • brain regions
  • cholinesterase inhibitors
  • energy metabolism
  • glucose metabolism
  • paraoxon
  • soman

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Biochemistry

Cite this

Cerebral metabolic effects of organophosphorus anticholinesterase compounds. / Miller, Alexander L; Medina, Miguel A.

In: Metabolic Brain Disease, Vol. 1, No. 2, 06.1986, p. 147-156.

Research output: Contribution to journalArticle

Miller, Alexander L ; Medina, Miguel A. / Cerebral metabolic effects of organophosphorus anticholinesterase compounds. In: Metabolic Brain Disease. 1986 ; Vol. 1, No. 2. pp. 147-156.
@article{97e7744271724f199baf4995341ac26a,
title = "Cerebral metabolic effects of organophosphorus anticholinesterase compounds",
abstract = "Rats treated intravenously with an organophosphoras anticholinesterase compound, paraoxon or soman, were sacrificed 2 to 131 min later, using 0.7sec of focused microwave irradiation (25 kW at 915 MHz). Brain regional rates of glucose utilization during 3-min intervals were determined with labeled glucose and fluorodeoxyglucase as tracers. Levels of glucose, lactate, ATP, and creatine phosphate were assayed in the same samples. The two compounds differed markedly in their effects on brain metabolism. Paraoxon (0.8LD50) depressed rates of glucose use in all brain regions, without causing consistent changes in brain metabolite levels. This depressant effect was most pronounced during the first 30 min after toxin exposure and had largely disappeared by 2hr. Soman (0.8-0.95 LD50) was variable in its effects. Animals that showed seizure-like behavior had marked increases in glucose use in diencephalon and cerebrum but no changes in cerebellum or brain stem. Rapid rates of glucose use were associated with high levels of lactic acid and lower levels of creatine phosphate. In cerebrum, but not diencephalon, levels of ATP fell by as much as 50{\%} in strongly affected animals by 30-130 min after soman. All of these effects were reversible with atropine. Soman-treated animals that did not have seizure-like activity did not exhibit these brain metabolic changes. These results and those of others show that cholinergic compounds vary greatly in their effects on brain glucose and energy metabolism. Although noncholinergic mechanisms are a possibility, the most parsimonious explanation for these findings is that cholinesterase inhibitors vary in their affinity for different central nervous system (CNS) acetylcholine receptor populations.",
keywords = "brain regions, cholinesterase inhibitors, energy metabolism, glucose metabolism, paraoxon, soman",
author = "Miller, {Alexander L} and Medina, {Miguel A.}",
year = "1986",
month = "6",
doi = "10.1007/BF00999384",
language = "English (US)",
volume = "1",
pages = "147--156",
journal = "Metabolic Brain Disease",
issn = "0885-7490",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Cerebral metabolic effects of organophosphorus anticholinesterase compounds

AU - Miller, Alexander L

AU - Medina, Miguel A.

PY - 1986/6

Y1 - 1986/6

N2 - Rats treated intravenously with an organophosphoras anticholinesterase compound, paraoxon or soman, were sacrificed 2 to 131 min later, using 0.7sec of focused microwave irradiation (25 kW at 915 MHz). Brain regional rates of glucose utilization during 3-min intervals were determined with labeled glucose and fluorodeoxyglucase as tracers. Levels of glucose, lactate, ATP, and creatine phosphate were assayed in the same samples. The two compounds differed markedly in their effects on brain metabolism. Paraoxon (0.8LD50) depressed rates of glucose use in all brain regions, without causing consistent changes in brain metabolite levels. This depressant effect was most pronounced during the first 30 min after toxin exposure and had largely disappeared by 2hr. Soman (0.8-0.95 LD50) was variable in its effects. Animals that showed seizure-like behavior had marked increases in glucose use in diencephalon and cerebrum but no changes in cerebellum or brain stem. Rapid rates of glucose use were associated with high levels of lactic acid and lower levels of creatine phosphate. In cerebrum, but not diencephalon, levels of ATP fell by as much as 50% in strongly affected animals by 30-130 min after soman. All of these effects were reversible with atropine. Soman-treated animals that did not have seizure-like activity did not exhibit these brain metabolic changes. These results and those of others show that cholinergic compounds vary greatly in their effects on brain glucose and energy metabolism. Although noncholinergic mechanisms are a possibility, the most parsimonious explanation for these findings is that cholinesterase inhibitors vary in their affinity for different central nervous system (CNS) acetylcholine receptor populations.

AB - Rats treated intravenously with an organophosphoras anticholinesterase compound, paraoxon or soman, were sacrificed 2 to 131 min later, using 0.7sec of focused microwave irradiation (25 kW at 915 MHz). Brain regional rates of glucose utilization during 3-min intervals were determined with labeled glucose and fluorodeoxyglucase as tracers. Levels of glucose, lactate, ATP, and creatine phosphate were assayed in the same samples. The two compounds differed markedly in their effects on brain metabolism. Paraoxon (0.8LD50) depressed rates of glucose use in all brain regions, without causing consistent changes in brain metabolite levels. This depressant effect was most pronounced during the first 30 min after toxin exposure and had largely disappeared by 2hr. Soman (0.8-0.95 LD50) was variable in its effects. Animals that showed seizure-like behavior had marked increases in glucose use in diencephalon and cerebrum but no changes in cerebellum or brain stem. Rapid rates of glucose use were associated with high levels of lactic acid and lower levels of creatine phosphate. In cerebrum, but not diencephalon, levels of ATP fell by as much as 50% in strongly affected animals by 30-130 min after soman. All of these effects were reversible with atropine. Soman-treated animals that did not have seizure-like activity did not exhibit these brain metabolic changes. These results and those of others show that cholinergic compounds vary greatly in their effects on brain glucose and energy metabolism. Although noncholinergic mechanisms are a possibility, the most parsimonious explanation for these findings is that cholinesterase inhibitors vary in their affinity for different central nervous system (CNS) acetylcholine receptor populations.

KW - brain regions

KW - cholinesterase inhibitors

KW - energy metabolism

KW - glucose metabolism

KW - paraoxon

KW - soman

UR - http://www.scopus.com/inward/record.url?scp=0022992594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022992594&partnerID=8YFLogxK

U2 - 10.1007/BF00999384

DO - 10.1007/BF00999384

M3 - Article

C2 - 3508239

AN - SCOPUS:0022992594

VL - 1

SP - 147

EP - 156

JO - Metabolic Brain Disease

JF - Metabolic Brain Disease

SN - 0885-7490

IS - 2

ER -