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Cyclooxygenase-1 mice show reduced neuroinflammation in response to beta-amyloid.

Choi SH, Bosetti F - Aging (Albany NY) (2009)

Bottom Line: Therefore, a full understanding of the physiological, pathological, and/or neuroprotective role of COX isoforms may help to develop better therapeutic strategies for the prevention or treatment of AD.In this study, we examined the effect of COX-1 genetic deletion on the inflammatory response and neurodegeneration induced by beta-amyloid. beta-amyloid (Abeta(1-42)) was centrally injected in the lateral ventricle of COX-1-deficient (COX-1(-/-)) and their respective wild-type (WT) mice.These results indicate that inhibition of COX-1 activity may be valid therapeutic strategy to reduce brain inflammatory response and neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Molecular Neuroscience Unit, Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.

ABSTRACT
Several independent epidemiological studies indicate that chronic use of non-steroidal anti-inflammatory drugs can reduce the risk of developing Alzheimer's disease (AD), supporting the inflammatory cascade hypothesis. Although the first clinical trial with indomethacin, a preferential cyclooxygenase (COX)-1 inhibitor, showed beneficial effects, subsequent large clinical trials, mostly using COX-2 inhibitors, failed to show any beneficial effect in AD patients with mild to severe cognitive impairment. These combined data suggest that either an early treatment is crucial to stop the mechanisms underlying the disease before the onset of the symptoms, or that preferential COX-1 inhibition, rather than COX-2, is beneficial. Therefore, a full understanding of the physiological, pathological, and/or neuroprotective role of COX isoforms may help to develop better therapeutic strategies for the prevention or treatment of AD. In this study, we examined the effect of COX-1 genetic deletion on the inflammatory response and neurodegeneration induced by beta-amyloid. beta-amyloid (Abeta(1-42)) was centrally injected in the lateral ventricle of COX-1-deficient (COX-1(-/-)) and their respective wild-type (WT) mice. In COX-1(-/-) mice, Abeta(1-42)-induced inflammatory response and neuronal damage were attenuated compared to WT mice, as shown by Fluoro-Jade B and nitrotyrosine staining. These results indicate that inhibition of COX-1 activity may be valid therapeutic strategy to reduce brain inflammatory response and neurodegeneration.

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Effects of COX-1 deficiency on PG production 24 h after Aβ 1-42 administration. Aβ1-42-injected                                            WT mice show significantly more PGE2                                            (A), PGF2α (B), and TXB2 levels (C)                                            than COX-1-/- mice. Mean ± SEM (n = 3-4 per                                            group); *P < 0.05, **P < 0.01                                            compared with the Aβ42-1-injected WT mice; #P                                            < 0.05, ##P < 0.01 compared with the Aβ1-42-injected                                            WT mice.
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Figure 5: Effects of COX-1 deficiency on PG production 24 h after Aβ 1-42 administration. Aβ1-42-injected WT mice show significantly more PGE2 (A), PGF2α (B), and TXB2 levels (C) than COX-1-/- mice. Mean ± SEM (n = 3-4 per group); *P < 0.05, **P < 0.01 compared with the Aβ42-1-injected WT mice; #P < 0.05, ##P < 0.01 compared with the Aβ1-42-injected WT mice.

Mentions: To determine the contribution of COX-1 to PG production after Aβ1-42 injection, we measured the levels of PGE2, PGF2α, and TXB2 24 h after Aβ1-42 administration. We observed significant reduction in levels of PGE2 (Figure 5A), PGF2α (Figure 5B), and TXB2 (Figure 5C) inAβ1-42-injected COX-1-/- mice.


Cyclooxygenase-1 mice show reduced neuroinflammation in response to beta-amyloid.

Choi SH, Bosetti F - Aging (Albany NY) (2009)

Effects of COX-1 deficiency on PG production 24 h after Aβ 1-42 administration. Aβ1-42-injected                                            WT mice show significantly more PGE2                                            (A), PGF2α (B), and TXB2 levels (C)                                            than COX-1-/- mice. Mean ± SEM (n = 3-4 per                                            group); *P < 0.05, **P < 0.01                                            compared with the Aβ42-1-injected WT mice; #P                                            < 0.05, ##P < 0.01 compared with the Aβ1-42-injected                                            WT mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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Figure 5: Effects of COX-1 deficiency on PG production 24 h after Aβ 1-42 administration. Aβ1-42-injected WT mice show significantly more PGE2 (A), PGF2α (B), and TXB2 levels (C) than COX-1-/- mice. Mean ± SEM (n = 3-4 per group); *P < 0.05, **P < 0.01 compared with the Aβ42-1-injected WT mice; #P < 0.05, ##P < 0.01 compared with the Aβ1-42-injected WT mice.
Mentions: To determine the contribution of COX-1 to PG production after Aβ1-42 injection, we measured the levels of PGE2, PGF2α, and TXB2 24 h after Aβ1-42 administration. We observed significant reduction in levels of PGE2 (Figure 5A), PGF2α (Figure 5B), and TXB2 (Figure 5C) inAβ1-42-injected COX-1-/- mice.

Bottom Line: Therefore, a full understanding of the physiological, pathological, and/or neuroprotective role of COX isoforms may help to develop better therapeutic strategies for the prevention or treatment of AD.In this study, we examined the effect of COX-1 genetic deletion on the inflammatory response and neurodegeneration induced by beta-amyloid. beta-amyloid (Abeta(1-42)) was centrally injected in the lateral ventricle of COX-1-deficient (COX-1(-/-)) and their respective wild-type (WT) mice.These results indicate that inhibition of COX-1 activity may be valid therapeutic strategy to reduce brain inflammatory response and neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Molecular Neuroscience Unit, Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.

ABSTRACT
Several independent epidemiological studies indicate that chronic use of non-steroidal anti-inflammatory drugs can reduce the risk of developing Alzheimer's disease (AD), supporting the inflammatory cascade hypothesis. Although the first clinical trial with indomethacin, a preferential cyclooxygenase (COX)-1 inhibitor, showed beneficial effects, subsequent large clinical trials, mostly using COX-2 inhibitors, failed to show any beneficial effect in AD patients with mild to severe cognitive impairment. These combined data suggest that either an early treatment is crucial to stop the mechanisms underlying the disease before the onset of the symptoms, or that preferential COX-1 inhibition, rather than COX-2, is beneficial. Therefore, a full understanding of the physiological, pathological, and/or neuroprotective role of COX isoforms may help to develop better therapeutic strategies for the prevention or treatment of AD. In this study, we examined the effect of COX-1 genetic deletion on the inflammatory response and neurodegeneration induced by beta-amyloid. beta-amyloid (Abeta(1-42)) was centrally injected in the lateral ventricle of COX-1-deficient (COX-1(-/-)) and their respective wild-type (WT) mice. In COX-1(-/-) mice, Abeta(1-42)-induced inflammatory response and neuronal damage were attenuated compared to WT mice, as shown by Fluoro-Jade B and nitrotyrosine staining. These results indicate that inhibition of COX-1 activity may be valid therapeutic strategy to reduce brain inflammatory response and neurodegeneration.

Show MeSH
Related in: MedlinePlus