Apolipoprotein E deficiency effects on learning in mice are dependent upon the background strain

Lominska, Chris; Levin, Justine A.; Wang, Jennifer; Sikes, John L.; Kao, Catherine; Smith, Jonathan

doi:10.1016/s0166-4328(00)00365-x

Cited by 15 publications

(11 citation statements)

References 47 publications

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“…The number of buried caps within the lesion was significantly higher in ruptured (2.66Ϯ0. 16) There was no statistically significant difference between ruptured and intact plaques in terms of media cross-sectional area (ruptured, 0.079Ϯ0.006 m 2 ; intact, 0.076Ϯ0.007 mm 2 ; Pϭ0.73).…”

Section: Plaque Characteristicsmentioning

confidence: 84%

“…The mice used in this study have a mixed background of C57BL/6 and 129SvJ, whereas most published studies make use of animals back- crossed through at least 10 generations onto a C57BL/6 background. The importance of strain differences to phenotypic expression has been highlighted in reports by Dansky et al 15 and Lominska et al 16 These studies compared apoE knockout mice on a C57BL/6 background with those on an FVB background. The extent of atherosclerosis was 7-to 9-fold greater in C57BL/6 mice than in FVB, despite lower total plasma cholesterol levels.…”

Section: Strain Differencesmentioning

confidence: 99%

“…The extent of atherosclerosis was 7-to 9-fold greater in C57BL/6 mice than in FVB, despite lower total plasma cholesterol levels. 15,16 Furthermore, 129Sv mice absorb dietary cholesterol more effectively than C57BL/6 mice. 17 Possibly an even more telling difference between these mouse strains is the platelet content of transforming growth factor ␤-1 (TGF-␤1), which is 4-fold higher in C57BL/6 mice than in 129Sv mice.…”

Section: Strain Differencesmentioning

confidence: 99%

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Characteristics of Intact and Ruptured Atherosclerotic Plaques in Brachiocephalic Arteries of Apolipoprotein E Knockout Mice

Williams

Johnson

Carson

et al. 2002

ATVB

209

178

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Abstract-The brachiocephalic arteries of fat-fed apolipoprotein E knockout mice develop plaques that frequently rupture and form luminal thromboses. The morphological characteristics of plaques without evidence of instability or with healed previous ruptures (intact) and vessels with acutely ruptured plaques (ruptured) have now been defined, to understand the process of plaque destabilization in more detail. Ninety-eight apolipoprotein E knockout mice were fed a diet supplemented with 21% lard and 0.15% cholesterol, for 5 to 59 weeks. Of these 98 mice, 51 had an acutely ruptured plaque in the brachiocephalic artery. See cover and page 713The apolipoprotein E (apoE) knockout mouse has become established as a model of hypercholesterolemia and atherosclerotic lesion development. 2-5 After 6 months on a high-fat diet, advanced fibrous plaques are observed with thin luminal elastin and collagen fibers capping small lipid-rich globular lesions. 5 Four studies have now reported that the lesions of apoE knockout mice can spontaneously become unstable. 6 -9 The brachiocephalic (also known as the innominate) artery, which is the first branch from the aortic arch, bifurcating to form the right common carotid artery and the right subclavian artery, is a site of predilection for the development of such vulnerable lesions. It provides a small and well-defined area in which to study the progressive loss of plaque stability and, eventually, rupture.In a previous study, 7 a small number of apoE knockout mice were examined. All of these had died suddenly, which meant that it was not possible to perfusion fix their arteries. In the current study, the development and morphology of brachiocephalic artery plaques have been characterized in a cohort of 98 apoE knockout mice. Ruptured and intact lesions have been compared both in animals dying suddenly and in those that were perfusion fixed after scheduled termination. Methods AnimalsHomozygous apoE knockout mice 10 were obtained from Charles River Laboratories (Manston, Kent, UK). The strain background of these animals was 50% C57BL/6, 50% 129SvJ, as determined by fingerprinting of tail-tip DNA. The housing and care of the animals and all the procedures used in these studies were performed in accordance with the guidelines and regulations of the University of Bristol and the United Kingdom Home Office. HusbandryStarting at 6 to 8 weeks of age, 98 apoE knockout mice (51 male) were fed a high-fat rodent diet containing 21% fat from lard and supplemented with 0.15% (wt/wt) cholesterol (Special Diets Services) for a period of 5 to 59 weeks. Cages were checked daily, and any animals that had suffered sudden death were immediately removed and processed for histological examination. TerminationAnimals were anesthetized by intraperitoneal injection of sodium pentobarbitone before exsanguination by arterial perfusion via the

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Section: Plaque Characteristicsmentioning

confidence: 84%

Section: Strain Differencesmentioning

confidence: 99%

Section: Strain Differencesmentioning

confidence: 99%

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Characteristics of Intact and Ruptured Atherosclerotic Plaques in Brachiocephalic Arteries of Apolipoprotein E Knockout Mice

Williams

Johnson

Carson

et al. 2002

ATVB

209

178

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“…It is thought that the differing results may be caused by differences in mouse strain or genetic background, housing conditions, life events, or nutrition (Lominska et al, 2001;Veinbergs and Masliah, 1999). We therefore subjected the mice to the Morris maze task and subsequently examined the integrity of the BBB.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E Protects against Neuropathology Induced by a High-Fat Diet and Maintains the Integrity of the Blood-Brain Barrier during Aging

Mulder

Blokland

Berg

et al. 2001

Laboratory Investigation

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SUMMARY:The present study provides evidence that chronic intake of a high-fat diet induces a dramatic extravasation of immunoglobulins, indicating alterations in blood-brain barrier (BBB) functioning, in the brains of apolipoprotein E (apoE)-knockout mice, but not of C57Bl/6 control mice. Using sodium fluorescein as a marker for the permeability of the BBB, we found additional support for age-related disturbances of BBB function in apoE-knockout mice. Behavioral analysis of apoE-knockout mice compared with C57Bl/6 mice indicated that they were also less efficient in acquiring the spatial Morris water maze task. Furthermore, apoE-knockout mice are known to develop severe atherosclerosis, which is exacerbated with a high-fat diet. We therefore compared the apoE-knockout mice with the apoE3-Leiden transgenic mice, which are known to develop atherosclerosis. However, apoE3-Leiden mice that were kept on a high-fat, high-cholesterol diet and that developed atherosclerosis to an extent similar to the apoE-knockout mice, showed no signs of BBB disturbances. These results indicate for the first time that apoE plays an essential role in the maintenance of the integrity of the BBB during aging and that it protects the brain from neuropathology induced by a high-fat diet. We therefore hypothesize that the role of apoE in the maintenance of the integrity of the BBB may be the mechanism by which apoE affects the progression of neurodegeneration, as seen in Alzheimer's disease. (Lab Invest 2001, 81:953-960).A polipoprotein E (apoE) is synthesized in almost all cell types and throughout the body. Within the brain, astrocytes are the predominant source of apoE (Pitas et al, 1987). It is thought that apoE functions by mediating neuronal repair and/or remodeling during development and during regeneration after injury to the central nervous system by mediating the distribution of lipids, predominantly cholesterol and phospholipids (Nathan et al, 1994).Three common human isoforms of apoE exist: E2, E3, and E4. ApoE4 is now a well-established risk factor for the development of Alzheimer's disease (AD) (Corder et al, 1993;Saunders et al, 1993). ApoE4 has also been associated with other neurological diseases, including vascular dementia and a poor clinical outcome in patients after stroke and head injury (Nicoll et al, 1995;Slooter et al, 1997). The mechanism by which apoE4 affects the process of neurodegeneration, however, is largely unknown.Mice deficient in apoE display disturbances in learning and memory function as well as in long-term potentiation (Krugers et al, 1997;Krzywkowski et al, 1999;Oitzl et al, 1997;Veinbergs and Masliah, 1999). They display several neuropathologic alterations, including a loss of synapses with increasing age, cytoskeletal alterations (Masliah et al, 1995), and a reduced activity of choline acetyltransferase (Gordon et al, 1995). In addition, they show an impaired response to ischemic, traumatic, and excitotoxic lesions (Chen et al, 1997;Laskowitz et al, 1997). On the contrary, a few studies report neit...

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“…Also, ApoE-deficient C57BL/6 mice showed impairment in learning while that of FVB/N mice did not show that impairment (Lominska et al 2001). Moreover, C57L and C57BL responded to estrogen administration by elevating their apoE protein level but C3H and BALB/c did not show any response (Srivastava et al 1997).…”

Section: Resultsmentioning

confidence: 92%

Age-Dependent Expression of Apolipoprotein E in Mouse Cerebral Cortex

Singh

Thakur

2010

J Mol Neurosci

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Apolipoprotein E (apoE) is predominantly a lipid transport protein involved in membrane repair and synaptic plasticity in brain. Its genotype is associated with late-onset sporadic and familial Alzheimer's disease (AD). Its expression increases when any injury takes place in the nervous system and in age-related disorders including AD. However, it is not clearly understood how the level of apoE changes in the normal aging brain. Therefore, we have analyzed the effect of age on apoE protein and mRNA level in the cerebral cortex of young, adult, and old male AKR strain mice. Western, northern, and RT-PCR results reveal that the level of apoE protein and mRNA is higher in young as compared to adult and then remains unchanged in old mouse cerebral cortex. This indicates that during normal aging, apoE level is maintained in old similar to adult and suggests involvement of other factors in maintaining apoE-mediated brain functions in old.

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Apolipoprotein E deficiency effects on learning in mice are dependent upon the background strain

Cited by 15 publications

References 47 publications

Characteristics of Intact and Ruptured Atherosclerotic Plaques in Brachiocephalic Arteries of Apolipoprotein E Knockout Mice

Characteristics of Intact and Ruptured Atherosclerotic Plaques in Brachiocephalic Arteries of Apolipoprotein E Knockout Mice

Apolipoprotein E Protects against Neuropathology Induced by a High-Fat Diet and Maintains the Integrity of the Blood-Brain Barrier during Aging

Age-Dependent Expression of Apolipoprotein E in Mouse Cerebral Cortex

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