Mouse Models of Cognitive Disorders in Trisomy 21: A Review

Sérégaza, Zohra; Roubertoux, Pierre L.; Jamon, Marc; Soumireu-Mourat, Bernard

doi:10.1007/s10519-006-9056-9

Cited by 65 publications

(51 citation statements)

References 75 publications

(65 reference statements)

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“…Sérégaza et al, 2006). In particular, previous studies have noted a decrease at early ages in immunostaining for choline acetyltransferase-positive (ChAT+) neurons in the medial septum in Ts65Dn mice (Granholm, Sanders and Crnic, 2000;Holtzman et al, 1996).…”

Section: General Conclusionmentioning

confidence: 96%

“…Thus, the present findings are generally consistent with many reports of memory impairments in this partial trisomy model of Down syndrome, most examining mice at 6 months and older (cf. Sérégaza et al, 2006). With multiple task-dependent neurobiological mechanisms involved in learning and memory, different tasks are likely to show different functional sensitivities and therefore different ages of onset of impairments.…”

Section: Spontaneous Alternationmentioning

confidence: 99%

“…Ts65Dn mice exhibit learning and memory deficits on several tasks, comprehensively reviewed in Sérégaza et al (2006). For example, impairments have been seen on spatial, operant conditioning and context discrimination tasks (Bimonte-Nelson et al, 2003;Demas et al, 1996Demas et al, , 1998Escoriheula et al, 1995Escoriheula et al, , 1998Reeves et al, 1995;Seo and Isacson, 2005;Wenger et al, 2004), as well as on tasks involving sustained attention (Driscoll et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Chang

Gold

2008

Neurobiology of Learning and Memory

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Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer's Disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22-25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 μg/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice.

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Section: General Conclusionmentioning

confidence: 96%

Section: Spontaneous Alternationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Chang

Gold

2008

Neurobiology of Learning and Memory

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“…145 During recent years, several murine models of DS have been generated, carrying triplications of different segments of Chr16, which has a high degree of synteny with human Chr21. 146,147 The most intensively studied mouse model of DS is the Ts65Dn line, 148 which summarizes the main hallmarks of the DS phenotype, including characteristic craniofacial abnormalities, impaired spatial and non-spatial learning abilities and attention deficits. [149][150][151][152][153][154] At the cellular level, Ts65Dn mice have a reduced number of hippocampal and cerebellar neurons, 155,156 impaired neurogenesis in the dentate gyrus of the hippocampus in both young and aged adults 157,158 and a prominent reduction in dendritic branching in several brain regions, accompanied by alterations in spine size and shape.…”

Section: Impact Of Ee On the Brain L Baroncelli Et Almentioning

confidence: 99%

Nurturing brain plasticity: impact of environmental enrichment

et al. 2009

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Environmental enrichment (EE) is known to profoundly affect the central nervous system (CNS) at the functional, anatomical and molecular level, both during the critical period and during adulthood. Recent studies focusing on the visual system have shown that these effects are associated with the recruitment of previously unsuspected neural plasticity processes. At early stages of brain development, EE triggers a marked acceleration in the maturation of the visual system, with maternal behaviour acting as a fundamental mediator of the enriched experience in both the foetus and the newborn. In adult brain, EE enhances plasticity in the cerebral cortex, allowing the recovery of visual functions in amblyopic animals. The molecular substrate of the effects of EE on brain plasticity is multi-factorial, with reduced intracerebral inhibition, enhanced neurotrophin expression and epigenetic changes at the level of chromatin structure. These findings shed new light on the potential of EE as a non-invasive strategy to ameliorate deficits in the development of the CNS and to treat neurological disorders.

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“…It is well-known that the brain is affected in all individuals with Trisomy 21 and that 56% of patients have heart defects . The MiR-155 and MiR-139 genes are close to APP, on the telomeric side, in a chromosomal region that is not involved in trisomic brain and cognitive difficulties (Sérégaza et al 2006).…”

Section: Rare Diseases May Share Common Pathophysiological Mechanismsmentioning

confidence: 99%

From Molecules to Behavior: Lessons from the Study of Rare Genetic Disorders

Roubertoux

Vries

2011

Behav Genet

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Rare diseases are defined as conditions with a prevalence of less than 1/2,000. To date between 6,000 and 7,000 rare diseases have been identified and many of those have manifestations that include intellectual disability, developmental disorders or other behavioural phenotypes. In this special issue we bring together a range of papers where rare diseases were used as models to delineate specific aspects of learning and memory, or behaviour. In this introductory paper we summarize some of the lessons we can learn from rare diseases. Firstly, we learn that, collectively, rare diseases are not at all rare. As many as 1 in 20 individuals may be affected by a rare disease at some point in their life. Secondly, we learn that rare diseases may share common pathophysiological mechanisms. A discovery in one can therefore have direct relevance to many others. A third lesson is that the study of rare diseases can lead to an understanding of common disorders, as exemplified by the relationship between Trisomy 21 (Down syndrome) and Alzheimer's disease. A fourth lesson from rare diseases is that the 'one gene-one functional consequence' assumption is not correct. Finally, rare diseases have shed new light on the strengths and weaknesses of animal models in the study of behavioural phenotypes.

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Mouse Models of Cognitive Disorders in Trisomy 21: A Review

Cited by 65 publications

References 75 publications

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Nurturing brain plasticity: impact of environmental enrichment

From Molecules to Behavior: Lessons from the Study of Rare Genetic Disorders

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