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Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome.

Galante M, Jani H, Vanes L, Daniel H, Fisher EM, Tybulewicz VL, Bliss TV, Morice E - Hum. Mol. Genet. (2009)

Bottom Line: Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour in cerebellum-dependent learning tasks that require high motor coordination and balance.In addition, basic electrophysiological properties of cerebellar circuitry and synaptic plasticity have been investigated.Our observations provide further evidence that support the validity of the Tc1 mouse as a model for DS, which will help us to provide insights into the causal factors responsible for motor deficits observed in persons with DS.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Pharmacologie de la Synapse, CNRS UMR 8619, Université Paris-Sud, 91405 Orsay Cedex, France.

ABSTRACT
Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of human chromosome 21 (Hsa21). Recently, O'Doherty et al. [An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 309 (2005) 2033-2037] generated a trans-species aneuploid mouse line (Tc1) that carries an almost complete Hsa21. The Tc1 mouse is the most complete animal model for DS currently available. Tc1 mice show many features that relate to human DS, including alterations in memory, synaptic plasticity, cerebellar neuronal number, heart development and mandible size. Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour in cerebellum-dependent learning tasks that require high motor coordination and balance. In addition, basic electrophysiological properties of cerebellar circuitry and synaptic plasticity have been investigated. Our results reveal that, compared with controls, Tc1 mice exhibit a higher spontaneous locomotor activity, a reduced ability to habituate to their environments, a different gait and major deficits on several measures of motor coordination and balance in the rota rod and static rod tests. Moreover, cerebellar long-term depression is essentially normal in Tc1 mice, with only a slight difference in time course. Our observations provide further evidence that support the validity of the Tc1 mouse as a model for DS, which will help us to provide insights into the causal factors responsible for motor deficits observed in persons with DS.

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Static rod performance of WT (white bars) and Tc1 (black bars) mice. Mice are scored for the time (s) they took to reach the home table (maximum time allowed: 5 min). The results show an increased latency in Tc1 mice. Values represent means ± S.E.M. *P < 0.05, compared with WT mice.
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DDP055F2: Static rod performance of WT (white bars) and Tc1 (black bars) mice. Mice are scored for the time (s) they took to reach the home table (maximum time allowed: 5 min). The results show an increased latency in Tc1 mice. Values represent means ± S.E.M. *P < 0.05, compared with WT mice.

Mentions: We next examined motor coordination of Tc1 mice on a static rod. To determine whether Tc1 and WT mice differed on their initial performance in this task, differences between groups in the latency to reach the table on day 1 were examined. There was no significant difference between the groups for this measure of initial motor skill. However, after an average of 10 days of training, our data also showed that Tc1 mice needed significantly more time to reach the home table (Fig. 2; F1,16=6.29, P = 0.05). Moreover, 19% of Tc1 mice, but only 4% of WT mice fell off the rod. We also noticed that Tc1 mice exhibit a great number of hindpaw slips on the static rod. Taken together, these results indicate impaired balance and coordination of movement in Tc1 mice. The analysis of the data was done after exclusion of trials during which the animal remained inactive on the rod. Interestingly, WT mice were more likely to participate in inactive behaviour. On a total of 90 trials per group, only two trials had to be excluded in Tc1 mice, whereas 14 trials were eliminated in WT mice.


Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome.

Galante M, Jani H, Vanes L, Daniel H, Fisher EM, Tybulewicz VL, Bliss TV, Morice E - Hum. Mol. Genet. (2009)

Static rod performance of WT (white bars) and Tc1 (black bars) mice. Mice are scored for the time (s) they took to reach the home table (maximum time allowed: 5 min). The results show an increased latency in Tc1 mice. Values represent means ± S.E.M. *P < 0.05, compared with WT mice.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2664148&req=5

DDP055F2: Static rod performance of WT (white bars) and Tc1 (black bars) mice. Mice are scored for the time (s) they took to reach the home table (maximum time allowed: 5 min). The results show an increased latency in Tc1 mice. Values represent means ± S.E.M. *P < 0.05, compared with WT mice.
Mentions: We next examined motor coordination of Tc1 mice on a static rod. To determine whether Tc1 and WT mice differed on their initial performance in this task, differences between groups in the latency to reach the table on day 1 were examined. There was no significant difference between the groups for this measure of initial motor skill. However, after an average of 10 days of training, our data also showed that Tc1 mice needed significantly more time to reach the home table (Fig. 2; F1,16=6.29, P = 0.05). Moreover, 19% of Tc1 mice, but only 4% of WT mice fell off the rod. We also noticed that Tc1 mice exhibit a great number of hindpaw slips on the static rod. Taken together, these results indicate impaired balance and coordination of movement in Tc1 mice. The analysis of the data was done after exclusion of trials during which the animal remained inactive on the rod. Interestingly, WT mice were more likely to participate in inactive behaviour. On a total of 90 trials per group, only two trials had to be excluded in Tc1 mice, whereas 14 trials were eliminated in WT mice.

Bottom Line: Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour in cerebellum-dependent learning tasks that require high motor coordination and balance.In addition, basic electrophysiological properties of cerebellar circuitry and synaptic plasticity have been investigated.Our observations provide further evidence that support the validity of the Tc1 mouse as a model for DS, which will help us to provide insights into the causal factors responsible for motor deficits observed in persons with DS.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Pharmacologie de la Synapse, CNRS UMR 8619, Université Paris-Sud, 91405 Orsay Cedex, France.

ABSTRACT
Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of human chromosome 21 (Hsa21). Recently, O'Doherty et al. [An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 309 (2005) 2033-2037] generated a trans-species aneuploid mouse line (Tc1) that carries an almost complete Hsa21. The Tc1 mouse is the most complete animal model for DS currently available. Tc1 mice show many features that relate to human DS, including alterations in memory, synaptic plasticity, cerebellar neuronal number, heart development and mandible size. Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour in cerebellum-dependent learning tasks that require high motor coordination and balance. In addition, basic electrophysiological properties of cerebellar circuitry and synaptic plasticity have been investigated. Our results reveal that, compared with controls, Tc1 mice exhibit a higher spontaneous locomotor activity, a reduced ability to habituate to their environments, a different gait and major deficits on several measures of motor coordination and balance in the rota rod and static rod tests. Moreover, cerebellar long-term depression is essentially normal in Tc1 mice, with only a slight difference in time course. Our observations provide further evidence that support the validity of the Tc1 mouse as a model for DS, which will help us to provide insights into the causal factors responsible for motor deficits observed in persons with DS.

Show MeSH
Related in: MedlinePlus