Early Alterations in Operant Performance and Prominent Huntingtin Aggregation in a Congenic F344 Rat Line of the Classical CAGn51truncModel of Huntington Disease

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Details zur Publikation

Autor(en): Plank AC, Canneva F, Raber KA, Urbach YK, Dobner J, Puchades M, Bjaalie JG, Gillmann C, Bäuerle T, Riess O, Nguyen HHP, von Hörsten S
Zeitschrift: Frontiers in Neuroscience
Jahr der Veröffentlichung: 2018
Band: 12
ISSN: 1662-4548
eISSN: 1662-453X


Abstract

The transgenic rat model of Huntington disease expressing a fragment of mutant HTT (tgHD rat) has been thoroughly characterized and reproduces hallmark symptoms of human adult-onset HD. Pursuing the optimization of this model for evaluation of translational therapeutic approaches, the F344 inbred rat strain was considered as advantageous genetic background for the expression of the HD transgenic construct. In the present study, a novel congenic line of the SPRDtgHD transgenic model of HD, carrying 51 CAG repeats, was generated on the F344 rat genetic background. To assess the behavioral phenotype, classical assays investigating motor function, emotion, and sensorimotor gating were applied, along with automated screening of metabolic and activity parameters as well as operant conditioning tasks. The neuropathological phenotype was analyzed by immunohistochemistry andex vivomagnetic resonance imaging. F344tgHD rats displayed markedly reduced anxiety-like behavior in the social interaction test and elevated impulsivity traits already at 3 months of age. Neuropathologically, reduced striatal volume and pronounced aggregation of mutant huntingtin in several brain regions were detected at later disease stage. In conclusion, the congenic F344tgHD model reproduces key aspects of the human HD phenotype, substantiating its value for translational therapeutic approaches.


FAU-Autoren / FAU-Herausgeber

Bäuerle, Tobias Prof. Dr.
Professur für Multimodale Bildgebung in der präklinischen Forschung
Gillmann, Clarissa Dr. rer. nat.
Radiologisches Institut
Plank, Anne-Christine
Professur für Experimentelle Biomedizin
von Hörsten, Stephan Prof. Dr.
Professur für Experimentelle Biomedizin


Autor(en) der externen Einrichtung(en)
Universitätsklinikum Tübingen
University of Oslo


Zitierweisen

APA:
Plank, A.-C., Canneva, F., Raber, K.A., Urbach, Y.K., Dobner, J., Puchades, M.,... von Hörsten, S. (2018). Early Alterations in Operant Performance and Prominent Huntingtin Aggregation in a Congenic F344 Rat Line of the Classical CAGn51truncModel of Huntington Disease. Frontiers in Neuroscience, 12. https://dx.doi.org/10.3389/fnins.2018.00011

MLA:
Plank, Anne-Christine, et al. "Early Alterations in Operant Performance and Prominent Huntingtin Aggregation in a Congenic F344 Rat Line of the Classical CAGn51truncModel of Huntington Disease." Frontiers in Neuroscience 12 (2018).

BibTeX: 

Zuletzt aktualisiert 2019-14-03 um 09:34