FGF2 and dual agonist of NCAM and FGF receptor 1, Enreptin, rescue neurite outgrowth loss in hippocampal neurons expressing mutated huntingtin proteins
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.
KeywordsHuntington disease Mutant huntingtin FGF2 Enreptin Neurite outgrowth Hippocampal neurons
The authors thank Claire Gudex, Department of Clinical Research, University of Southern Denmark, for proofreading the manuscript.
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.
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.
- Bartus RT, Baumann TL, Brown L, Kruegel BR, Ostrove JM, Herzog CD (2013) Advancing neurotrophic factors as treatments for age-related neurodegenerative diseases: developing and demonstrating “clinical proof-of-concept” for AAV-neurturin (CERE-120) in Parkinson’s disease. Neurobiol Aging 34(1):35–61CrossRefGoogle Scholar
- Maksimović ID, Jovanović MD, Colić M, Mihajlović R, Mićić D, Selaković V et al (2001) Oxidative damage and metabolic dysfunction in experimental Huntington’s disease: selective vulnerability of the striatum and hippocampus. Vojnosanit Pregl 58(3):237–242Google Scholar
- Quarrell OWJ, Nance MA (2009) The diagnostic challenge. In: Quarrell OWJ, Brewer HM, Squitieri F, Barker RA, Nance MA, Landwehrmeyer BG (eds) Juvenile Huntington’s Disease and Other Trinucleotide Repeat Disorders. Oxford University Press, New YorkGoogle Scholar
- Sonn K, Pankratova S, Korshunova I, Zharkovsky A, Bock E, Berezin V, Kiryushko D (2010) A metallothionein mimetic peptide protects neurons against kainic acid-induced excitotoxicity. J Neurosci Res 88(5):1074–1082Google Scholar
- Zufferey R, Dull T, Mandel RJ, Bukovsky A, Quiroz D, Naldini L et al (1998) Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol 72(12):9873–9880Google Scholar