Overexpression of NMDAR2B in an inflammatory model of Alzheimer's disease: modulation by NOS inhibitors
| dc.Affiliation | October University for modern sciences and Arts (MSA) | |
| dc.contributor.author | Maher, Ahmed | |
| dc.contributor.author | Salah-Eldine El-Sayed, Nesrine | |
| dc.contributor.author | Breitinger, Hans-Georg | |
| dc.contributor.author | Zakaria Gad, Mohamed | |
| dc.date.accessioned | 2020-01-30T08:52:10Z | |
| dc.date.available | 2020-01-30T08:52:10Z | |
| dc.date.issued | 2014 | |
| dc.description | MSA Google Scholar | en_US |
| dc.description.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. | en_US |
| dc.description.sponsorship | Elsevier | en_US |
| dc.description.uri | https://www.scimagojr.com/journalsearch.php?q=14347&tip=sid&clean=0 | |
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| dc.identifier.doi | https://doi.org/10.1016/j.brainresbull.2014.10.007 | |
| dc.identifier.other | https://doi.org/10.1016/j.brainresbull.2014.10.007 | |
| dc.identifier.uri | https://t.ly/LMn8X | |
| dc.language.iso | en | en_US |
| dc.publisher | Elsevier | en_US |
| dc.relation.ispartofseries | Brain research bulletin;Volume: 109 Pages: 109-116 | |
| dc.subject | University of Alzheimer; Nitric; oxide; NMDAR; NOS; inhibitors; Diflunisal; LPS | en_US |
| dc.title | Overexpression of NMDAR2B in an inflammatory model of Alzheimer's disease: modulation by NOS inhibitors | en_US |
| dc.type | Article | en_US |
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