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Neuroendocrine Alterations in the Fragile X Mouse

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Modeling Fragile X Syndrome

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 54))

Abstract

The expression of GABAA receptors in the fragile X mouse brain is significantly downregulated. We additionally found that the expression of somatostatin and voltage-sensitive calcium channels (VSCCs) is also reduced. GABAA and the VSCCs, through a synergistic interaction, perform a critical role in mediating activity-dependent developmental processes. In the developing brain, GABA is excitatory and its actions are mediated through GABAA receptors. Subsequent to GABA-mediated depolarization, the VSCCs are activated and intracellular calcium is increased, which mediates gene transcription and other cellular events. GABAergic excitation mediated through GABAA receptors and the subsequent activation of the VSCCs are critically important for the establishment of neuronal connectivity within immature neuronal networks. Data from our laboratories suggest that there is a dysregulation of axonal pathfinding during development in the fragile X mouse brain and that this is likely due to a dysregulation of the synergistic interactions of GABA and VSCC. Thus, we hypothesize that the altered expression of these critical channels in the early stages of brain development leads to altered activity-dependent gene expression that may potentially lead to the developmental delay characteristic of the fragile X syndrome.

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Acknowledgments

Support for this project was provided by FRAXA research foundation and PSC-CUNY to AEI. The authors wish to thank Francoise Sidime and Lorenz Neuwirth for their assistance with the glucose tolerance test, and the staff of the College of Staten Island’s vivarium.

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Authors and Affiliations

  1. Department of Biology, College of Staten Island, 2800 Victory Blvd, Staten Island, 10314, USA

    Abdeslem El Idrissi & William L’Amoreaux

  2. Center for Developmental Neuroscience and Developmental Disabilities CSI/IBR, Staten Island, NY, USA

    Abdeslem El Idrissi, Xin Yan, William L’Amoreaux, W. Ted Brown & Carl Dobkin

  3. Doctoral Program in Biology – Neuroscience, City University of New York, 365 Fifth Avenue, New York, NY, 10016, USA

    Abdeslem El Idrissi, Xin Yan & William L’Amoreaux

  4. Advanced Imaging Facility, CSI, Staten Island, NY, USA

    William L’Amoreaux

  5. Department of Human Genetics, Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 10314, USA

    W. Ted Brown & Carl Dobkin

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  1. Abdeslem El Idrissi
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Correspondence to Abdeslem El Idrissi .

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  1. New York State Institute for Basic Resea, Forest Hill Road 1050, Staten Island, 10314, USA

    Robert B. Denman

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Idrissi, A.E., Yan, X., L’Amoreaux, W., Brown, W.T., Dobkin, C. (2012). Neuroendocrine Alterations in the Fragile X Mouse. In: Denman, R. (eds) Modeling Fragile X Syndrome. Results and Problems in Cell Differentiation, vol 54. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21649-7_11

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