Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model

Hirata-Fukae, Chiho; Li, Hui Fang; Hoe, Hyang Sook; Gray, Audrey; Minami, S. Sakura; Hamada, Katsuyoshi; Niikura, Takako; Hua, Fang; Tsukagoshi-Nagai, Hiroe; Horikoshi-Sakuraba, Yuko; Mughal, Mohamed R.; Rebeck, G. William; LaFerla, Frank M.; Mattson, Mark P.; Iwata, Nobuhisa; Saido, Takaomi C.; Klein, William L.; Duff, Karen; Aisen, Paul S.; Matsuoka, Yasuji

doi:10.1016/j.brainres.2008.03.079

Cited by 244 publications

(221 citation statements)

References 59 publications

Supporting

Mentioning

180

Contrasting

Order By: Relevance

“…Both protective activities are likely, but we did not find robust A␤ labeling at 9 months in the line of 3xTg-AD mice on the diets used. This line showed limited intraneuronal labeling but lacked plaques at 9 months (data not shown), consistent with a recent report on the same "low expressing" line (Hirata-Fukae et al, 2008).…”

Section: Discussionsupporting

confidence: 92%

-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin

Yang²,

Rosario³

et al. 2009

Journal of Neuroscience

481

332

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 92%

-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin

Yang²,

Rosario³

et al. 2009

Journal of Neuroscience

481

332

View full text Add to dashboard Cite

show abstract

“…Therefore, we treated 3xTg-AD mice for 18 weeks, starting at 10 months of age, assuming these mice had already developed cognitive impairment, as published previously. However, since our study was conducted, a genetic drift has been observed in this line of mice outside of the LaFerla laboratory (Hirata-Fukae et al, 2008). At the time of our study, the 3xTg-AD mice in our colony developed plaque deposition between 10 and 12 months, but we did not run a pretest to determine whether they were already cognitively impaired before the onset of L-NBP treatment.…”

Section: Methodsmentioning

confidence: 99%

L-3-n-Butylphthalide Improves Cognitive Impairment and Reduces Amyloid- in a Transgenic Model of Alzheimer's Disease

Peng¹,

Sun²,

Hon³

et al. 2010

Journal of Neuroscience

126

View full text Add to dashboard Cite

Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, and personality changes. L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been demonstrated to have neuroprotective effects on ischemic, vascular dementia, and amyloid-␤ (A␤)-infused animal models. In the current study, we examined the effects of L-NBP on learning and memory in a triple-transgenic AD mouse model (3xTg-AD) that develops both plaques and tangles with aging, as well as cognitive deficits. Ten-month-old 3xTg-AD mice were given 15 mg/kg L-NBP by oral gavage for 18 weeks. L-NBP treatment significantly improved learning deficits, as well as long-term spatial memory, compared with vehicle control treatment. L-NBP treatment significantly reduced total cerebral A␤ plaque deposition and lowered A␤ levels in brain homogenates but had no effect on fibrillar A␤ plaques, suggesting preferential removal of diffuse A␤ deposits. Furthermore, we found that L-NBP markedly enhanced soluble amyloid precursor protein secretion (␣APPs), ␣-secretase, and PKC␣ expression but had no effect on steady-state full-length APP. Thus, L-NBP may direct APP processing toward a non-amyloidogenic pathway and preclude A␤ formation in the 3xTg-AD mice. The effect of L-NBP on regulating APP processing was further confirmed in neuroblastoma SK-N-SH cells overexpressing wild-type human APP 695 (SK-N-SH APPwt). L-NBP treatment in 3xTg-AD mice also reduced glial activation and oxidative stress compared with control treatment. L-NBP shows promising preclinical potential as a multitarget drug for the prevention and/or treatment of Alzheimer's disease.

show abstract

“…17 These mice were aged to 18 months, because that is the age that amyloid plaque deposition and tau pathology begin to appear in this colony. Mice were housed at the Georgetown University animal facility in a temperaturecontrolled room at 22 C and were kept on a 12-hour light/12-hour dark cycle.…”

Section: Micementioning

confidence: 99%

Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma

Winston

Noël

Neustadtl

et al. 2016

The American Journal of Pathology

View full text Add to dashboard Cite

Mild traumatic brain injury (mTBI) is an emerging risk for chronic behavioral, cognitive, and neurodegenerative conditions. Athletes absorb several hundred mTBIs each year; however, rodent models of repeat mTBI (rmTBI) are often limited to impacts in the single digits. Herein, we describe the effects of 30 rmTBIs, examining structural and pathological changes in mice up to 365 days after injury. We found that single mTBI causes a brief loss of consciousness and a transient reduction in dendritic spines, reflecting a loss of excitatory synapses. Single mTBI does not cause axonal injury, neuroinflammation, or cell death in the gray or white matter. Thirty rmTBIs with a 1-day interval between each mTBI do not cause dendritic spine loss; however, when the interinjury interval is increased to 7 days, dendritic spine loss is reinstated. Thirty rmTBIs cause white matter pathology characterized by positive silver and Fluoro-Jade B staining, and microglial proliferation and activation. This pathology continues to develop through 60 days, and is still apparent at 365 days, after injury. However, rmTBIs did not increase b-amyloid levels or tau phosphorylation in the 3xTg-AD mouse model of Alzheimer disease. Our data reveal that single mTBI causes a transient loss of synapses, but that rmTBIs habituate to repetitive injury within a short time period. rmTBI causes the development of progressive white matter pathology that continues for months after the final impact. (Am J Pathol 2016, 186: 552e567; http://dx.doi.org/ 10.1016/j.ajpath.2015 Athletes participating in contact sports are at high risk of exposure to large numbers of concussive and subconcussive mild traumatic brain injuries (mTBIs). Recent studies using head impact telemetry systems have begun to reveal how many head impacts an individual football player can receive in the process of playing his or her sport. In a study of high school football players, the number of helmet impacts >20 g recorded in a single season ranged from a low of 226 (average, 4.7 per session) to a high of 1855 (average, 38.6 per session). 1 Most of these impacts do not result in the clinical diagnosis of a concussion; however, it is not known if the cumulative effects of these impacts can result in increased damage to the brain. mTBI has been extensively modeled in mice and rats. 2 Most of these rodent models use fewer than five mTBIs, and report adverse events, including intracerebral bleeding, skull fractures, severe axonal injury, neuronal cell death, and increased mortality.

show abstract

Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model

Cited by 244 publications

References 59 publications

-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin

-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin

L-3-n-Butylphthalide Improves Cognitive Impairment and Reduces Amyloid- in a Transgenic Model of Alzheimer's Disease

Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma

Contact Info

Product

Resources

About