Overexpression of NMDAR2B in an inflammatory model of Alzheimer's disease: modulation by NOS inhibitors
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Date
2014
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Elsevier
Series Info
Brain research bulletin;Volume: 109 Pages: 109-116
Scientific Journal Rankings
Abstract
Background:Alzheimer’sdisease (AD)is a commonformof age-relateddementia, characterizedbydeposition of amyloid A plaques, neuroinflammation and neurodegeneration. N-methyl-d-aspartate receptors
(NMDAR) are postsynaptic glutamate receptors that play a role in memory formation and are targets for
memantadine, an anti-AD drug. Nitric oxide (NO) signaling has been involved in both memory development through neuronal NO synthase (nNOS), and neuroinflammation through inducible NO synthase
(iNOS) which mediates CNS inflammatory processes.
Aim: To study the expression of the NMDAR2B subunit in an inflammatory model of AD before and after
treatment with NO modulators.
Materials and methods: AD was induced in mice by a single dose of lipopolysaccharide (LPS). Behavioral
tests for spatial and non-spatial memories and locomotor activity were performed to assess disease severity and progression. The effects of l-NAME (general NOS inhibitor), 1400W (iNOS inhibitor), diflunisal
(systemic anti-inflammatory drug that does not cross the blood brain barrier), and l-arginine, the substrate for NOS was determined. Immunohistochemistry was done to confirm AD and brain lysates were
tested for A formation, levels of NMDAR2B subunits, and brain NO levels.
Results: Systemic LPS induced AD, as shown by cognitive impairment; increased levels of A and concomitant increase in the brain NO concentrations. This was associated with overexpression of NMDAR2B.
All tested drugs improved behavioral dysfunction, prevented A formation and NMDAR overexpression,
and lead to decrease in NO concentration in the brain. l-Arginine alone, however, did not produce similar
improvements.
Conclusion: NMDAR2B subunits are overexpressed in an inflammatory model of AD and NO inhibitors
ameliorate this expression.
Description
MSA Google Scholar
Keywords
University of Alzheimer; Nitric; oxide; NMDAR; NOS; inhibitors; Diflunisal; LPS
Citation
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