Age-related deficits in mice performing working memory tasks in a water maze.

Magnusson, Kathy R.; Scruggs, Brandi; Aniya, Jennifer; Wright, Karl C.; Ontl, Todd A.; Xing, Yiding; Bai, Lijun

doi:10.1037/0735-7044.117.3.485

Cited by 65 publications

(59 citation statements)

References 48 publications

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“…Lack of improvement in the delayed working memory trials was observed only in the case of 26-month old mice. Similar results were obtained in our previous experiment with C57BL/6 mice where middle-aged mice performed well in the delayed working memory trials but the old mice were impaired (Magnusson et al, 2003). To study working memory in rats using the water maze, several investigators have considered using multiple trials within one session to represent working memory (Galea et al, 2000;Kikusui et al, 1999;Lehmann et al, 2000), whereas several others have used only the first trial after a naïve swim (Frick et al, 1995;Morris et al, 1986;Steele and Morris, 1999).…”

Section: Reference and Working Memory Performancesupporting

confidence: 70%

“…Frick and coworkers have shown that out of the four trials in working memory tasks, trials 1 and 2 were associated with working memory and trials 4 and 5 were more associated with reference memory (Frick et al, 1995). In our previous experiment we used trial 4 as the delayed trial, but it was not clear if the mice were using working memory for that trial (Magnusson et al, 2003). In the present study we used the second trial (next trial after naïve swim) as the delayed trial (10 minutes delay after naïve swim) and found similar results in both middle-aged and old mice.…”

Section: Reference and Working Memory Performancementioning

confidence: 99%

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Relationship between mRNA expression of splice forms of the ζ1 subunit of the N-methyl-d-aspartate receptor and spatial memory in aged mice

Das

Magnusson

2008

Brain Research

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Age-related changes in the protein and mRNA expression of some of the splice forms of the ζ1 (NR1) subunit of the NMDA receptor have been seen in mice and rats. The present study was designed to determine whether individual splice forms of the ζ1 subunit of the NMDA receptor within prefrontal/frontal cortical regions contribute to memory deficits during aging and whether experience in learning tasks can influence the expression of the splice forms. mRNA expression of 4 splice forms (ζ1-1, ζ1-3, ζ1-a and ζ1-b) and mRNA for all known splice forms (ζ1-pan) were examined by in situ hybridization. mRNA for C-terminal splice forms, ζ1-1 (+C1 and +C2 cassettes) and ζ1-3 (+C1 and +C2′), showed significant declines during aging in several brain regions even though overall ζ1-pan mRNA expression was not significantly affected by aging. This suggests that these splice forms are more influenced by aging than the subunit as a whole. There was an increase in the expression of ζ1-a (−N1 cassette) splice form in the behaviorally-experienced old mice relative to the younger groups. Old mice with high levels of mRNA expression for the ζ1-a splice form in orbital cortex showed the best performances in the working memory task, but the poorest performances in the cued, associative learning task. These results suggest that there is a complex interaction between ζ1 splice form expression and performance of memory tasks during aging.

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Section: Reference and Working Memory Performancesupporting

confidence: 70%

Section: Reference and Working Memory Performancementioning

confidence: 99%

Relationship between mRNA expression of splice forms of the ζ1 subunit of the N-methyl-d-aspartate receptor and spatial memory in aged mice

Das

Magnusson

2008

Brain Research

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“…Robust spatial learning impairments in the aged AL rats were evident on all dependent measures during training and the probe test. These results are consistent with much previous research, demonstrating age-related deficits in cognitive function [4,8,36].…”

Section: Discussionsupporting

confidence: 83%

“…Aging rodents have been shown to be a promising animal model for studying memory deficits. In particular, tasks of spatial memory have been employed [1][2][3][4][5][6][7][8] with clearly demonstrated deficits in aged rats as a model associated with aging humans [9][10][11]. Deficits that accompany the decline of spatial learning and memory in aged rats include a loss of visual acuity [12], thermoregulatory control [3], impairments in sensorimotor behavior [6,8,13], and the development of lesions and diseases [14].…”

mentioning

confidence: 99%

Effects of chronic adult dietary restriction on spatial learning in the aged F344×BN hybrid F1 rat

Fitting¹,

Booze²,

Gilbert³

et al. 2008

Physiology & Behavior

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Dietary restriction (DR) has been shown to increase life span and reduce disease incidence across a variety of species. Recent research suggests that chronic adult DR may also alter age-related cognitive decline. The purpose of this study was twofold: (1) to examine the potential deficits in spatial learning ability in the aged F344 X BN hybrid F1 rat with specific attention to the contributory effects of motoric impairments and (2) to determine the influence of chronic adult DR on any such impairments. The Morris water maze (MWM) task was employed with a 1.8 m diameter tank, 10 cm 2 escape platform, 28°C water, and an automated collapsing central starting platform. Spatial learning impairments in the aged rats were evident on all dependent measures during training and the probe test. Motoric function, as reflected in measures of strength and locomotion demonstrated profound age-related performance impairments that were attenuated by chronic adult DR. The present data also replicate previous reports, indicating that DR attenuates the age-related impairments of performance in the MWM as indexed by the latency measure in acquisition, but critically was dissociated from any DR effect on measures of preference and, more critically, accuracy in the probe test. Collectively, the most parsimonious interpretation of DR effects on MWM performance would appear to be the preservation of motoric, and not cognitive, function. KeywordsCognition; Motoric function; Morris water maze One of the more disconcerting age-related changes across a variety of species is a decline in learning and memory. Aging rodents have been shown to be a promising animal model for studying memory deficits. In particular, tasks of spatial memory have been employed [1][2][3][4][5][6][7][8] with clearly demonstrated deficits in aged rats as a model associated with aging humans [9][10][11]. Deficits that accompany the decline of spatial learning and memory in aged rats include a loss of visual acuity [12], thermoregulatory control [3], impairments in sensorimotor behavior [6,8,13], and the development of lesions and diseases [14]. These

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“…Age-related changes in complex tasks, such as the spatial version of the water maze, are well documented and have been shown to occur as a function of strain (Gower et al, 1993;Ingram et al, 1999: Frick et al, 2000Magnusson et al, 2003). The wild-type F1 hybrids performed well in all behavioral paradigms evaluated, consistent with hybrid vigor (Owen et al, 1997), and displayed few significant age-related behavioral changes.…”

Section: Discussionmentioning

confidence: 70%

Astrogliosis and behavioral changes in mice lacking the neutral cysteine protease bleomycin hydrolase

et al. 2007

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Bleomycin hydrolase is a multifaceted neutral cysteine protease with a suggested role in antigen presentation, homocysteine-thiolactone metabolism, and Alzheimer's disease pathogenesis. Deletion of the protease in mice results in increased neonatal mortality and dermatopathology. Immunohistochemical and behavioral studies of BLMH knockout mice were undertaken to further evaluate the role of the protease in the brain. No gross abnormalities in the central nervous system were observed upon preliminary histological examination of B6.129Blmh tm1Geh /J null animals. However, glial fibrillary acid protein immunohistochemistry revealed a global reactive astrogliosis in the aged null animals, indicative of undefined brain pathology. The role of BLMH in the brain was further explored by characterizing the behavioral phenotype of hybrid [129S6-Blmh tm1Geh /J X B6.129 Blmh tm1Geh /J]F1 null and littermate controls using multiple behavioral paradigms. In the water maze, deletion of BLMH resulted in poorer performance during water maze probe trials without detectable effect of the mutation on sensorimotor function. In addition, no age-dependent decline in discriminative performance on probe trials was observed in null animals. These data suggest a physiological non-redundant function for BLMH in the central nervous system. Keywords knockout; hippocampus; learning; memory; aging; Alzheimer's disease Bleomycin hydrolase (BLMH) is a highly conserved and unusual aminopeptidase with suggested importance in antigen presentation, homocysteine-thiolactone metabolism, and Alzheimer's disease (AD). A genetic polymorphism within the conserved carboxyterminal region of BLMH is a susceptibility locus for sporadic AD and has been reported by us (Montoya et al., 1998) and others (Papassotiropoulos et al., 2000) to be associated with an approximate two-fold increased risk for development of the disease, although this effect has not been replicated in all studies. Accumulation of β-amyloid peptide derived from proteolytic cleavage of the amyloid precursor protein is believed to be a critical event in the early pathogenesis of Correspondence should be addressed to: John S. Lazo, Department of Pharmacology, University of Pittsburgh, Biomedical Science Tower 3, Suite 10040, 3501 Fifth Avenue, Pittsburgh, PA 15260, E-mail: lazo@pitt.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 November 22. Published in final edited form as:Neuroscience. AD (Hardy and Allsop, 1991;Hardy and Higgins, 1992). In vitro st...

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Age-related deficits in mice performing working memory tasks in a water maze.

Cited by 65 publications

References 48 publications

Relationship between mRNA expression of splice forms of the ζ1 subunit of the N-methyl-d-aspartate receptor and spatial memory in aged mice

Relationship between mRNA expression of splice forms of the ζ1 subunit of the N-methyl-d-aspartate receptor and spatial memory in aged mice

Effects of chronic adult dietary restriction on spatial learning in the aged F344×BN hybrid F1 rat

Astrogliosis and behavioral changes in mice lacking the neutral cysteine protease bleomycin hydrolase

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