Poul Henning Jensen

A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats

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A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats. / Nuber, Silke; Harmuth, Florian; Kohl, Zacharias; Adame, Anthony; Trejo, Margaritha; Schönig, Kai; Zimmermann, Frank; Bauer, Claudia; Casadei, Nicolas; Giel, Christiane; Calaminus, Carsten; Pichler, Bernd J; Jensen, Poul Henning; Müller, Christian; Amato, Davide; Kornhuber, Johannes; Teismann, Peter; Yamakado, Hodaka; Takahashi, Ryosuke; Winkler, Juergen; Masliah, Eliezer; Riess, Olaf.

In: Brain, Vol. 136, No. Pt 2, 2013, p. 412-32.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Nuber, S, Harmuth, F, Kohl, Z, Adame, A, Trejo, M, Schönig, K, Zimmermann, F, Bauer, C, Casadei, N, Giel, C, Calaminus, C, Pichler, BJ, Jensen, PH, Müller, C, Amato, D, Kornhuber, J, Teismann, P, Yamakado, H, Takahashi, R, Winkler, J, Masliah, E & Riess, O 2013, 'A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats', Brain, vol. 136, no. Pt 2, pp. 412-32. https://doi.org/10.1093/brain/aws358

APA

Nuber, S., Harmuth, F., Kohl, Z., Adame, A., Trejo, M., Schönig, K., Zimmermann, F., Bauer, C., Casadei, N., Giel, C., Calaminus, C., Pichler, B. J., Jensen, P. H., Müller, C., Amato, D., Kornhuber, J., Teismann, P., Yamakado, H., Takahashi, R., ... Riess, O. (2013). A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats. Brain, 136(Pt 2), 412-32. https://doi.org/10.1093/brain/aws358

CBE

Nuber S, Harmuth F, Kohl Z, Adame A, Trejo M, Schönig K, Zimmermann F, Bauer C, Casadei N, Giel C, Calaminus C, Pichler BJ, Jensen PH, Müller C, Amato D, Kornhuber J, Teismann P, Yamakado H, Takahashi R, Winkler J, Masliah E, Riess O. 2013. A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats. Brain. 136(Pt 2):412-32. https://doi.org/10.1093/brain/aws358

MLA

Vancouver

Author

Nuber, Silke ; Harmuth, Florian ; Kohl, Zacharias ; Adame, Anthony ; Trejo, Margaritha ; Schönig, Kai ; Zimmermann, Frank ; Bauer, Claudia ; Casadei, Nicolas ; Giel, Christiane ; Calaminus, Carsten ; Pichler, Bernd J ; Jensen, Poul Henning ; Müller, Christian ; Amato, Davide ; Kornhuber, Johannes ; Teismann, Peter ; Yamakado, Hodaka ; Takahashi, Ryosuke ; Winkler, Juergen ; Masliah, Eliezer ; Riess, Olaf. / A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats. In: Brain. 2013 ; Vol. 136, No. Pt 2. pp. 412-32.

Bibtex

@article{e99c2da0bf7c4fb29d9f0f69b5e1a0c3,
title = "A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats",
abstract = "Conversion of soluble α-synuclein into insoluble and fibrillar inclusions is a hallmark of Parkinson's disease and other synucleinopathies. Accumulating evidence points towards a relationship between its generation at nerve terminals and structural synaptic pathology. Little is known about the pathogenic impact of α-synuclein conversion and deposition at nigrostriatal dopaminergic synapses in transgenic mice, mainly owing to expression limitations of the α-synuclein construct. Here, we explore whether both the rat as a model and expression of the bacterial artificial chromosome construct consisting of human full-length wild-type α-synuclein could exert dopaminergic neuropathological effects. We found that the human promoter induced a pan-neuronal expression, matching the rodent α-synuclein expression pattern, however, with prominent C-terminally truncated fragments. Ageing promoted conversion of both full-length and C-terminally truncated α-synuclein species into insolube and proteinase K-resistant fibres, with strongest accumulation in the striatum, resembling biochemical changes seen in human Parkinson's disease. Transgenic rats develop early changes in novelty-seeking, avoidance and smell before the progressive motor deficit. Importantly, the observed pathological changes were associated with severe loss of the dopaminergic integrity, thus resembling more closely the human pathology.",
author = "Silke Nuber and Florian Harmuth and Zacharias Kohl and Anthony Adame and Margaritha Trejo and Kai Sch{\"o}nig and Frank Zimmermann and Claudia Bauer and Nicolas Casadei and Christiane Giel and Carsten Calaminus and Pichler, {Bernd J} and Jensen, {Poul Henning} and Christian M{\"u}ller and Davide Amato and Johannes Kornhuber and Peter Teismann and Hodaka Yamakado and Ryosuke Takahashi and Juergen Winkler and Eliezer Masliah and Olaf Riess",
year = "2013",
doi = "10.1093/brain/aws358",
language = "English",
volume = "136",
pages = "412--32",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "Pt 2",

}

RIS

TY - JOUR

T1 - A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats

AU - Nuber, Silke

AU - Harmuth, Florian

AU - Kohl, Zacharias

AU - Adame, Anthony

AU - Trejo, Margaritha

AU - Schönig, Kai

AU - Zimmermann, Frank

AU - Bauer, Claudia

AU - Casadei, Nicolas

AU - Giel, Christiane

AU - Calaminus, Carsten

AU - Pichler, Bernd J

AU - Jensen, Poul Henning

AU - Müller, Christian

AU - Amato, Davide

AU - Kornhuber, Johannes

AU - Teismann, Peter

AU - Yamakado, Hodaka

AU - Takahashi, Ryosuke

AU - Winkler, Juergen

AU - Masliah, Eliezer

AU - Riess, Olaf

PY - 2013

Y1 - 2013

N2 - Conversion of soluble α-synuclein into insoluble and fibrillar inclusions is a hallmark of Parkinson's disease and other synucleinopathies. Accumulating evidence points towards a relationship between its generation at nerve terminals and structural synaptic pathology. Little is known about the pathogenic impact of α-synuclein conversion and deposition at nigrostriatal dopaminergic synapses in transgenic mice, mainly owing to expression limitations of the α-synuclein construct. Here, we explore whether both the rat as a model and expression of the bacterial artificial chromosome construct consisting of human full-length wild-type α-synuclein could exert dopaminergic neuropathological effects. We found that the human promoter induced a pan-neuronal expression, matching the rodent α-synuclein expression pattern, however, with prominent C-terminally truncated fragments. Ageing promoted conversion of both full-length and C-terminally truncated α-synuclein species into insolube and proteinase K-resistant fibres, with strongest accumulation in the striatum, resembling biochemical changes seen in human Parkinson's disease. Transgenic rats develop early changes in novelty-seeking, avoidance and smell before the progressive motor deficit. Importantly, the observed pathological changes were associated with severe loss of the dopaminergic integrity, thus resembling more closely the human pathology.

AB - Conversion of soluble α-synuclein into insoluble and fibrillar inclusions is a hallmark of Parkinson's disease and other synucleinopathies. Accumulating evidence points towards a relationship between its generation at nerve terminals and structural synaptic pathology. Little is known about the pathogenic impact of α-synuclein conversion and deposition at nigrostriatal dopaminergic synapses in transgenic mice, mainly owing to expression limitations of the α-synuclein construct. Here, we explore whether both the rat as a model and expression of the bacterial artificial chromosome construct consisting of human full-length wild-type α-synuclein could exert dopaminergic neuropathological effects. We found that the human promoter induced a pan-neuronal expression, matching the rodent α-synuclein expression pattern, however, with prominent C-terminally truncated fragments. Ageing promoted conversion of both full-length and C-terminally truncated α-synuclein species into insolube and proteinase K-resistant fibres, with strongest accumulation in the striatum, resembling biochemical changes seen in human Parkinson's disease. Transgenic rats develop early changes in novelty-seeking, avoidance and smell before the progressive motor deficit. Importantly, the observed pathological changes were associated with severe loss of the dopaminergic integrity, thus resembling more closely the human pathology.

U2 - 10.1093/brain/aws358

DO - 10.1093/brain/aws358

M3 - Journal article

C2 - 23413261

VL - 136

SP - 412

EP - 432

JO - Brain

JF - Brain

SN - 0006-8950

IS - Pt 2

ER -