Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer’s disease in a sex-dimorphic pattern

Melnikova, Tatiana; Savonenko, Alena; Wang, Q.; Liang, Xin; Hand, T.; Wu, Liejun; Kaufmann, Walter E.; Vehmas, Anne K.; Andreasson, Katrin I.

doi:10.1016/j.neuroscience.2006.05.001

Cited by 127 publications

(91 citation statements)

References 78 publications

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“…Considering the animal AD models, the effect of NSADIs has been investigated in genetically modified mice models and in the STZ-icv rat model, however conflicting results have been obtained. Overexpression of COX-2 in APPswe-PS1dE9 mice AD model resulted in specific deficits in spatial working memory in female but not male mice and these sexspecific deficits were abolished by pharmacological inhibition of COX-2 by celecoxibe, in the absence of significant changes in amyloid burden (Melnikova et al 2006). Data indicates that COX-2 activity promotes cognitive deficits in a sex-dependent but amyloid burden-independent manner in this mice AD model.…”

Section: Drugs With Predominant Anti-inflammatory Activitymentioning

confidence: 63%

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

et al. 2012

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Section: Drugs With Predominant Anti-inflammatory Activitymentioning

confidence: 63%

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

et al. 2012

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“…No significant group differences occurred in either test. The effect of ATCV-1 exposure on learning and memory was then tested using the Y-maze test to evaluate spatial recognition memory (17,18). Mice exposed to ATCV-1 performed at a lower level on this test compared with control mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice

Yolken

Jones‐Brando

Dunigan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Chloroviruses (family Phycodnaviridae) are large DNA viruses known to infect certain eukaryotic green algae and have not been previously shown to infect humans or to be part of the human virome. We unexpectedly found sequences homologous to the chlorovirus Acanthocystis turfacea chlorella virus 1 (ATCV-1) in a metagenomic analysis of DNA extracted from human oropharyngeal samples. These samples were obtained by throat swabs of adults without a psychiatric disorder or serious physical illness who were participating in a study that included measures of cognitive functioning. The presence of ATCV-1 DNA was confirmed by quantitative PCR with ATCV-1 DNA being documented in oropharyngeal samples obtained from 40 (43.5%) of 92 individuals. The presence of ATCV-1 DNA was not associated with demographic variables but was associated with a modest but statistically significant decrease in the performance on cognitive assessments of visual processing and visual motor speed. We further explored the effects of ATCV-1 in a mouse model. The inoculation of ATCV-1 into the intestinal tract of 9-11-wk-old mice resulted in a subsequent decrease in performance in several cognitive domains, including ones involving recognition memory and sensory-motor gating. ATCV-1 exposure in mice also resulted in the altered expression of genes within the hippocampus. These genes comprised pathways related to synaptic plasticity, learning, memory formation, and the immune response to viral exposure.chlorovirus ATCV-1 | infection | cognitive functioning | oropharyngeal virome | metagenomic sequencing

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“…After centrifugation (15,000 ϫ g, 10 min, 4°C), 20 l of the supernatant was injected onto a C-18 reverse-phase column (Spheri-5, RP-18, 4.6 mm ϫ 25 cm catecholamine column; BASi). The mobile phase consisted of 0.15 M chloroacetic acid, 0.2 mM (Crawley, 1999) was used to test novelty-induced exploration and anxiety levels as described previously (Laird et al, 2005;Melnikova et al, 2006). Briefly, the round, white openfield arena had a diameter of 100 cm and 55-cm-high sidewalls.…”

Section: Methodsmentioning

confidence: 99%

Amyloid Pathology Is Associated with Progressive Monoaminergic Neurodegeneration in a Transgenic Mouse Model of Alzheimer's Disease

Liu¹,

Yoo²,

Savonenko³

et al. 2008

J. Neurosci.

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177

169

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␤-Amyloid (A␤) pathology is an essential pathogenic component in Alzheimer's disease (AD). However, the significance of A␤ pathology, including A␤ deposits/oligomers and glial reactions, to neurodegeneration is unclear. In particular, despite the A␤ neurotoxicity indicated by in vitro studies, mouse models with significant A␤ deposition lack robust and progressive loss of forebrain neurons. Such results have fueled the view that A␤ pathology is insufficient for neurodegeneration in vivo. In this study, because monoaminergic (MAergic) neurons show degenerative changes at early stages of AD, we examined whether the APPswe/PS1⌬E9 mouse model recapitulates progressive MAergic neurodegeneration occurring in AD cases. We show that the progression forebrain A␤ deposition in the APPswe/ PS1⌬E9 model is associated with progressive losses of the forebrain MAergic afferents. Significantly, axonal degeneration is associated with significant atrophy of cell bodies and eventually leads to robust loss (ϳ50%) of subcortical MAergic neurons. Degeneration of these neurons occurs without obvious local A␤ or tau pathology at the subcortical sites and precedes the onset of anxiety-associated behavior in the mice. Our results show that a transgenic mouse model of A␤ pathology develops progressive MAergic neurodegeneration occurring in AD cases.

show abstract

Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer’s disease in a sex-dimorphic pattern

Cited by 127 publications

References 78 publications

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice

Amyloid Pathology Is Associated with Progressive Monoaminergic Neurodegeneration in a Transgenic Mouse Model of Alzheimer's Disease

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