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Altered calcium currents and axonal growth in Nf1 haploinsufficient mice

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Translational Neuroscience

Abstract

Mutations of the neurofibromin gene (NF1) cause neurofibromatosis type 1 (NF1), a disease in which learning disabilities are common. Learning deficits also are observed in mice with a heterozygous mutation of Nf1 (Nf1 +/−). Dysregulation of regulated neurotransmitter release has been observed in Nf1 +/− mice. However, the role of presynaptic voltage-gated Ca2+ channels mediating this release has not been investigated. We investigated whether Ca2+ currents and transmitter release were affected by reduced neurofibromin in Nf1 +/− mice. Hippocampal Ca2+ current density was greater in neurons from Nf1 +/− mice and a greater fraction of Ca2+ currents was activated at less depolarized potentials. In addition, release of the excitatory neurotransmitter, glutamate, was increased in neuronal cortical cultures from Nf1 +/− mice. Dendritic complexity and axonal length were also increased in neurons Nf1 +/− mice compared to wild-type neurons, linking loss of neurofibromin to developmental changes in hippocampal axonal/cytoskeletal dynamics. Collectively, these results show that altered Ca2+ channel density and transmitter release, along with increased axonal growth may account for the abnormal nervous system functioning in NF1.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Yuying Wang, Cynthia M. Hingtgen & Rajesh Khanna

  2. Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Cynthia M. Hingtgen

  3. Department of Indiana Spinal Cord and Brain Injury Research Group, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Rajesh Khanna

  4. Department of Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Joel M. Brittain, Sarah M. Wilson, Cynthia M. Hingtgen & Rajesh Khanna

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  1. Yuying Wang
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  2. Joel M. Brittain
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  3. Sarah M. Wilson
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  4. Cynthia M. Hingtgen
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  5. Rajesh Khanna
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Correspondence to Rajesh Khanna.

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These authors contributed equally

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Wang, Y., Brittain, J.M., Wilson, S.M. et al. Altered calcium currents and axonal growth in Nf1 haploinsufficient mice. Translat.Neurosci. 1, 106–114 (2010). https://doi.org/10.2478/v10134-010-0025-8

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  • DOI: https://doi.org/10.2478/v10134-010-0025-8

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