Characterization of synaptic dysfunction in an in vitro corticostriatal model system of Huntington’s disease

  • D. N. Artamonov
  • V. V. Korzhova
  • J. Wu
  • P. D. Rybalchenko
  • K. Im
  • V. A. Krasnoborova
  • O. L. Vlasova
  • I. B. Bezprozvanny
Articles
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Abstract

Huntington’s disease (HD) is an autosomal-dominant inherited neurodegenerative disease resulting from expanded amino acid (CAG) repeat in the gene that encodes protein huntingtin (Htt). HD remains incurable for now. A lot of evidence implicates aberrant synaptic connection between cortical and striatal neurons, a key component of HD pathophysilogy, which also leads to cognitive decline and motor disorders. In the present work synaptic activity between cortical and striatal neurons was studied on the corticostriatal co-culture model system of HD. Culture was prepared from HD mouse model YAC128. It was shown that first impairment appears on day 14 in vitro. Interestingly, these alterations occur in cortical neurons. Their activity in YAC128 cultures was higher than in cultures of wild-type neurons. At the same time, there were no differences in morphology of spines in striatal neurons. However, using novel optogenetic approach, we demonstrated that synaptic connections are already dysfunctional in YAC128 cultures. On day 19 in vitro the activity of cortical neurons in YAC128 cultures was reduced, which led to alterations on the post-synaptic side. Dendric spines of medium spiny neurons transformed and disappeared, which is possibly the main reason of neurodegenerative mechanisms during the HD development.

Keywords

synaptic transmission Huntington’s disease optogenetics dendritic spines neuronal culture 

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Copyright information

© Pleiades Publishing, Ltd. 2013

Authors and Affiliations

  • D. N. Artamonov
    • 1
  • V. V. Korzhova
    • 1
  • J. Wu
    • 2
  • P. D. Rybalchenko
    • 1
  • K. Im
    • 2
  • V. A. Krasnoborova
    • 1
  • O. L. Vlasova
    • 1
  • I. B. Bezprozvanny
    • 1
    • 2
  1. 1.Laboratory of Molecular NeurodegenerationSt. Petersburg Polytechnic UniversitySt. PetersburgRussia
  2. 2.Department of PhysiologyUniversity of Texas Southwestern Medical CenterDallasUSA

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