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Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down’s syndrome

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Down’s syndrome (DS), with an incidence of one in 800 live births, is the most common genetic disorder associated with mental retardation. This trisomy on chromosome 21 induces a variable phenotype in which the only common feature is the presence of mental retardation. The neural mechanisms underlying mental retardation might include defects in the formation of neuronal networks and neural plasticity. DS patients have alterations in the morphology, the density and the distribution of dendritic spines in the pyramidal neurons of the cortex. Our hypothesis is that the deficits in dendritic arborization observed in the principal neurons of DS patients and Ts65Dn mice (a model for DS that mimics most of the structural alterations observed in humans) may be mediated to some extent by changes in their inhibitory inputs. Different types of interneurons control different types of inhibition. Therefore, to understand well the changes in inhibition in DS, it is necessary to study the different types of interneurons separately. We have studied the expression of synaptophysin, Glutamic acid decarboxylase-67 (GAD-67) and calcium-binding protein-expressing cells in the primary somatosensory cortex of 4–5 month old Ts65Dn mice. We have observed an increment of GAD67 immunoreactivity that is related mainly to an increment of calretinin-immunoreactive cells and among them the ones with bipolar morphology. Since there is a propensity for epilepsy in DS patients, this increase in interneurons might reflect an attempt by the system to block overexcitation rather than an increment in total inhibition and could explain the deficit in interneurons and principal cells observed in elderly DS patients.

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Acknowledgments

This study was funded by Spanish Ministry of Education and Science (BFU2006-07313/BFI and BFU2007-64130/BFI); Foundation Jerome Lejeune and The Stanley Medical Research Institute (08R-2007).

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Authors and Affiliations

  1. Department of Cell Biology, University of Valencia, Dr Moliner Street, 50, 46100, Burjassot, Valencia, Spain

    D. Pérez-Cremades, S. Hernández, J. M. Blasco-Ibáñez, C. Crespo, J. Nacher & E. Varea

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  1. D. Pérez-Cremades
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  2. S. Hernández
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  3. J. M. Blasco-Ibáñez
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  4. C. Crespo
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  6. E. Varea
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Correspondence to E. Varea.

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Pérez-Cremades, D., Hernández, S., Blasco-Ibáñez, J.M. et al. Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down’s syndrome. J Neural Transm 117, 445–455 (2010). https://doi.org/10.1007/s00702-010-0376-9

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  • DOI: https://doi.org/10.1007/s00702-010-0376-9

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