The aged mouse as a model of cognitive decline with special emphasis on studies in NMRI mice

Gower, Alma J.; Lamberty, Yves

doi:10.1016/0166-4328(93)90132-a

Cited by 94 publications

(52 citation statements)

References 47 publications

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“…Analysis of dwell time in the target quadrant across age for wild-type animals only revealed a significant decline of performance consistent with age-dependent changes in performance on this task observed by others (Gower et al, 1993;von Bohlen und Halbach et al, 2006). Interestingly, no significant change across age was observed when a similar analysis was applied to the data of the young and aged null animals only.…”

Section: Discussionsupporting

confidence: 82%

“…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: 89%

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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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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 89%

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

et al. 2007

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“…Though no other work has evaluated the effect of 5-HT6R blockade on the consolidation of spatial recognition memory in aged animals, our results are consistent with previous studies in the rat that demonstrate an improvement of task acquisition and recall in a spatial learning paradigm in 20-and 22-month-old rats following acute or chronic 5-HT6R antagonism (Foley et al, 2004;Hirst et al, 2006). These age-related deficits, consistent with previous studies on spatial memory (Bach et al, 1999;Barnes, 1979;Pelleymounter, 1988, Gower andLamberty, 1993;Granger et al, 1996), are attributable to dysfunctions in memory processes on the basis that impaired locomotor activity in the two-trial place recognition test in the Y-maze could not be mistaken for a memory deficit because the test is based on the choice between a novel place and familiar places (Dellu et al, 1992(Dellu et al, , 2000 and the percentage of time spent in exploration is used as the measure. Indeed, in our hands, exploratory behavior was found to be only slightly reduced in the hole-board test (Table 2), and such an effect can probably be linked to the decrease in spontaneous locomotor activity (Table 1).…”

Section: -Ht6r Blockade Improves Memory V Da Silva Costa Et Alsupporting

confidence: 82%

Selective 5-HT6 Receptor Blockade Improves Spatial Recognition Memory and Reverses Age-Related Deficits in Spatial Recognition Memory in the Mouse

Costa

Duchatelle²,

Boulouard³

et al. 2008

Neuropsychopharmacol

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Studies have recently suggested that blockade of 5-HT6 receptors (5-HT6R) improves memory processes. As episodic memory alteration is one of the first deficits observed during normal aging and in neurological and neuropsychiatric disorders (Alzheimer's disease, schizophrenia), the present study sought to characterize the effects of 5-HT6R blockade on spatial recognition memory, which can be considered as 'episodic-like' memory, in rodents. We quantified the effects of the selective 5-HT6R antagonist SB-271046 (10 mg/kg, i.p.), using the two-trial place recognition task in the Y-maze, on acquisition, consolidation, and retrieval of spatial recognition memory in young adult mice (6-week-old; intertrial intervals (ITIs) 30, 60, 120, 240, and 360 min) and on the consolidation of spatial recognition memory in aged mice (3-, 12-, 18-, and 21-month-old; ITI 60 and 240 min). SB-271046-treated young adult mice explored the new arm more after a 240-min (pre-acquisition) and 360-min (post-acquisition) ITI, whereas vehicle-treated animals failed to discriminate the new arm when the ITI exceeded 120 min (pre-acquisition) or 240 min (post-acquisition). Aged mice, which expressed spatial memory deficits, explored the new arm more after a 60-min ITI (21-month-old) and a 240-min ITI (18-and 21-month-old) when treated with SB-271046. Consequently, 5-HT6R blockade improves spatial recognition memory in adult mice and reverses age-related consolidation deficits of episodic-like memory. This study provides further support for the use of 5-HT6R antagonists in the treatment of episodic memory disorders related to aging as well as neurological disorders such as Alzheimer's disease and schizophrenia.

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“…Many experiments examine individual differences in memory in aged rodents by identifying memoryimpaired versus unimpaired rats at single time points, often in the swim task (Gallagher and Nicolle 1993;Gallagher and Rapp 1997). However, the memory-impaired rats identified with this method of assessment are not always matched by impairments on other tasks (Markowska et al 1989;Lamberty and Gower 1992;Gower and Lamberty 1993). Perhaps individual differences would be more coherent across tasks if the rates of forgetting were examined, as compared with the more usual single memory tests at a fixed time after training.…”

Section: Discussionmentioning

confidence: 99%

Rapid forgetting of social transmission of food preferences in aged rats: Relationship to hippocampal CREB activation

Countryman¹,

Gold²

2007

Learn. Mem.

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A major characteristic of age-related changes in memory in rodents is an increase in the rate of forgetting of new information, even when tests given soon after training reveal intact memory. Interference with CREB functions similarly results in rapid decay of memory. Using quantitative immunocytochemistry, the present experiment examined the number of CREB-and pCREB-immunoreactive neurons in three regions of the dorsal and ventral hippocampus (dentate gyrus, CA3, and CA1) as a function of age and training. Rats were trained in a social transmission of food preference task. Using different food pairings, memory was tested in each rat immediately and 1, 2, 3, and 7 d later. Both young and old rats had intact and comparable memory scores at the immediate and 24-h tests, but old rats exhibited more rapid forgetting thereafter relative to that of young rats. The main findings were that training resulted in large increases in the number of pCREB-immunoreactive cells throughout the hippocampus in both young and aged rats. However, particularly in the ventral hippocampus, the training-elicited increase in pCREB-positive neurons was significantly lower in old than in young rats. Based on Western blot analyses in a separate set of rats, CREB levels were not responsive to training but were lower in the ventral hippocampus of old rats than of young rats. The present findings suggest that lower activation of CREB after training may contribute to the rapid forgetting seen in aged rats.Rats and mice exhibit age-related impairments in learning and memory on many tasks. Often, the impairments can be characterized in terms of rapid forgetting, in which aged rats and mice have relatively comparable learning and memory on tests soon after training, but poor memory at later times after training (Barnes and McNaughton 1985;

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The aged mouse as a model of cognitive decline with special emphasis on studies in NMRI mice

Cited by 94 publications

References 47 publications

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

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

Selective 5-HT6 Receptor Blockade Improves Spatial Recognition Memory and Reverses Age-Related Deficits in Spatial Recognition Memory in the Mouse

Rapid forgetting of social transmission of food preferences in aged rats: Relationship to hippocampal CREB activation

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