Intra- and intertask relationships in a behavioral test battery given to Tg2576 transgenic mice and controls

Arendash, Gary W.; King, David L

doi:10.1016/s0031-9384(02)00640-6

Cited by 45 publications

(25 citation statements)

References 24 publications

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“…The mechanisms underlying these impairments might differ from those causing more selective spatial learning deficits quantitatively, qualitatively, or both. The visible and hidden platform components of the water maze test can involve overlapping cognitive functions (7). Extensions of deficits from one component to the other might have been fostered here by the visibility of extramaze cues and the small size of the marker indicating the platform location during cued trials (see Supporting Text), which could promote engagement of spatial learning mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Alzheimer's disease (AD), the most frequent of these conditions, causes inexorable loss of memory and other cognitive functions. Although the etiology of most AD cases remains elusive, the analysis of related transgenic (TG) mouse models is beginning to unravel the pathogenic importance of specific AD-associated molecules (2)(3)(4)(5)(6)(7)(8). These models are also used increasingly to assess novel AD treatments (9)(10)(11)(12)(13).…”

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confidence: 99%

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Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits

Palop

Jones

Kekonius

et al. 2003

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

367

375

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Transgenic mice expressing human amyloid precursor proteins (hAPP) and amyloid-␤ peptides (A␤) in neurons develop phenotypic alterations resembling Alzheimer's disease (AD). The mechanisms underlying cognitive deficits in AD and hAPP mice are largely unknown. We have identified two molecular alterations that accurately reflect AD-related cognitive impairments. Learning deficits in mice expressing familial AD-mutant hAPP correlated strongly with decreased levels of the calcium-binding protein calbindin-D 28k (CB) and the calcium-dependent immediate early gene product c-Fos in granule cells of the dentate gyrus, a brain region critically involved in learning and memory. These molecular alterations were age-dependent and correlated with the relative abundance of A␤1-42 but not with the amount of A␤ deposited in amyloid plaques. CB reductions in the dentate gyrus primarily reflected a decrease in neuronal CB levels rather than a loss of CB-producing neurons. CB levels were also markedly reduced in granule cells of humans with AD, even though these neurons are relatively resistant to AD-related cell death. Thus, neuronal populations resisting cell death in AD and hAPP mice can still be drastically altered at the molecular level. The tight link between A␤-induced cognitive deficits and neuronal depletion of CB and c-Fos suggests an involvement of calcium-dependent pathways in AD-related cognitive decline and could facilitate the preclinical evaluation of novel AD treatments.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits

Palop

Jones

Kekonius

et al. 2003

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

367

375

View full text Add to dashboard Cite

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“…Lack of spatial memory was detected at 7 months in the MWM task (Lesne et al 2006). Arendash and King (2002) also found impairment in an active avoidance task and Corcoran et al (2002) in the forced alternation T-maze and Pavovlian fear-conditioning paradigms in contextual testing.…”

Section: Tg2576 Mouse Linementioning

confidence: 93%

APP Transgenic Mice: Their Use and Limitations

Balducci

Forloni

2010

Neuromol Med

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Alzheimer's disease is the most widespread form of dementia. Its histopathological hallmarks include vascular and extracellular β-amyloid (Aβ) deposition and intraneuronal neurofibrillary tangles (NFTs). Gradual decline of cognitive functions linked to progressive synaptic loss makes patients unable to store new information in the earlier stages of the pathology, later becoming completely dependent because they are unable to do even elementary daily life actions. Although more than a hundred years have passed since Alois Alzheimer described the first case of AD, and despite many years of intense research, there are still many crucial points to be discovered in the neuropathological pathway. The development of transgenic mouse models engineered with overexpression of the amyloid precursor protein carrying familial AD mutations has been extremely useful. Transgenic mice present the hallmarks of the pathology, and histological and behavioural examination supports the amyloid hypothesis. As in human AD, extracellular Aβ deposits surrounded by activated astrocytes and microglia are typical features, together with synaptic and cognitive defects. Although animal models have been widely used, they are still being continuously developed in order to recapitulate some missing aspects of the disease. For instance, AD therapeutic agents tested in transgenic mice gave encouraging results which, however, were very disappointing in clinical trials. Neuronal cell death and NFTs typical of AD are much harder to replicate in these mice, which thus offer a fundamental but still imperfect tool for understanding and solving dementia pathology.

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“…In some studies of targeted mutations [25,38] it is the only task employed, and in studies involving more than one test of spatial memory, it is almost always included in the battery [1,14,29,34,54]. Because the mouse cannot see the submerged platform and the maze itself is perfectly symmetrical, the animal must utilize asymmetrical extra-maze visual cues in order to become proficient.…”

Section: Introductionmentioning

confidence: 99%

Different rankings of inbred mouse strains on the Morris maze and a refined 4-arm water escape task

Wahłsten

Cooper

Crabbe³

2005

Behavioural Brain Research

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The submerged platform or Morris water escape task is widely used to study genetic variation in spatial learning and memory, but interpretation is sometimes difficult because of wall hugging, jumping off the platform, floating or non-spatial swim strategies. We modified the task by introducing four wide arms into the circular tank and adding features that reduced, eliminated, or compensated for several competing behaviors. Three versions of the 4-arm task were evaluated in detail, and the third version yielded good results for six of eight inbred strains. Furthermore, the 4-arm task could be scored adequately without computerized video tracking. Although performance on the 4-arm task was generally superior to the Morris maze, the extent of the improvement was strain dependent. Two strains with retinal degeneration (C3H/HeJ, FVB/NJ) performed poorly on both the Morris and 4-arm mazes, whereas C57BL/6J and DBA/2J did well on both mazes. A/J performed poorly on the Morris task but became very proficient on the 4-arm maze, despite its strong tendency to hug the walls of the tank. The BALB/cByJ strain, on the other hand, exhibited the best probe trial performance on the Morris maze but was very slow in acquiring the 4-arm task. We conclude that no single task can reveal the full richness of spatially guided behavior in a wide range of mouse genotypes.

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Intra- and intertask relationships in a behavioral test battery given to Tg2576 transgenic mice and controls

Cited by 45 publications

References 24 publications

Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits

Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits

APP Transgenic Mice: Their Use and Limitations

Different rankings of inbred mouse strains on the Morris maze and a refined 4-arm water escape task

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