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FGF2 and dual agonist of NCAM and FGF receptor 1, Enreptin, rescue neurite outgrowth loss in hippocampal neurons expressing mutated huntingtin proteins

  • Mirolyuba IlievaEmail author
  • Troels T. Nielsen
  • Tanja Michel
  • Stanislava Pankratova
Psychiatry and Preclinical Psychiatric Studies - Original Article

Abstract

In the present study, we developed an in vitro model of Huntington disease (HD) by transfecting primary rat hippocampal neurons with plasmids coding for m-htt exon 1 with different number of CAG repeats (18, 50 and 115) and demonstrated the influence of the length of polyQ sequence on neurite elongation. We found that exogenously applied FGF2 significantly rescued the m-htt-induced loss of neurite outgrowth. Moreover, the Enreptin peptide, an FGFR1 and NCAM dual agonist, had a similar neuritogenic effect to FGF2 in clinically relevant m-htt 50Q-expressing neurons. This study has developed an in vitro model of primary hippocampal neurons transfected with m-htt-coding vectors that is a powerful tool to study m-htt–related effects on neuronal placticity.

Keywords

Huntington disease Mutant huntingtin FGF2 Enreptin Neurite outgrowth Hippocampal neurons 

Notes

Acknowledgements

The authors thank Claire Gudex, Department of Clinical Research, University of Southern Denmark, for proofreading the manuscript.

Funding

The project was supported by the Velux Foundation.

Compliance with ethical standards

Conflict of interest

The authors state that there is no conflict of interest relevant to this article, nor has it previously been published.

Bioethics

Animals were treated in accordance with the Danish Animal Welfare Act, and the study was approved by the Department of Experimental Medicine at the University of Copenhagen.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Psychiatry, Department of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
  2. 2.Psychiatry in the Region of Southern DenmarkOdense University HospitalOdenseDenmark
  3. 3.Laboratory of Neural Plasticity, Department of NeuroscienceUniversity of CopenhagenCopenhagenDenmark
  4. 4.Danish Dementia Research Center, Department of Neurology, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
  5. 5.Research Laboratory for Stereology and NeuroscienceBispebjerg-Frederiksberg Hospital, Copenhagen University HospitalCopenhagenDenmark
  6. 6.BRIDGE - Brain Research - Inter-Disciplinary Guided Excellence, Department of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark

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