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Title: Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

Abstract

Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hours after endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (2-3 fold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (>50 percent) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition ({approx}25 percent decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Director, Office of Science; National Institutes of Health (US)
OSTI Identifier:
808920
Report Number(s):
LBNL-50356
Journal ID: ISSN 0022-3042; JONRA9; R&D Project: 445401; B& R KP1401040; TRN: US200307%%119
DOE Contract Number:  
AC03-76SF00098
Resource Type:
Journal Article
Journal Name:
Journal of Neurochemistry
Additional Journal Information:
Journal Volume: 82; Journal Issue: 4; Other Information: Journal Publication Date: Aug. 2002; PBD: 10 Dec 2001; Journal ID: ISSN 0022-3042
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ANIMALS; ANTIOXIDANTS; AUTORADIOGRAPHY; BRAIN; CRYOSTATS; DISEASES; DRINKING WATER; ENDOTOXINS; HIPPOCAMPUS; INDUCTION; LIPOPOLYSACCHARIDES; AUTORADIOGRAPHY GLUTAMATE

Citation Formats

Biegon, A, Alvarado, M, Budinger, T F, Grossman, R, Hensley, K, West, M S, Kotake, Y, Ono, M, and Floyd, R A. Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain. United States: N. p., 2001. Web.
Biegon, A, Alvarado, M, Budinger, T F, Grossman, R, Hensley, K, West, M S, Kotake, Y, Ono, M, & Floyd, R A. Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain. United States.
Biegon, A, Alvarado, M, Budinger, T F, Grossman, R, Hensley, K, West, M S, Kotake, Y, Ono, M, and Floyd, R A. 2001. "Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain". United States.
@article{osti_808920,
title = {Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain},
author = {Biegon, A and Alvarado, M and Budinger, T F and Grossman, R and Hensley, K and West, M S and Kotake, Y and Ono, M and Floyd, R A},
abstractNote = {Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hours after endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (2-3 fold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (>50 percent) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition ({approx}25 percent decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.},
doi = {},
url = {https://www.osti.gov/biblio/808920}, journal = {Journal of Neurochemistry},
issn = {0022-3042},
number = 4,
volume = 82,
place = {United States},
year = {Mon Dec 10 00:00:00 EST 2001},
month = {Mon Dec 10 00:00:00 EST 2001}
}