Cerebral Dopamine Neurotrophic Factor Diffuses Around the Brainstem and Does Not Undergo Anterograde Transport After Injection to the Substantia Nigra
Cerebral dopamine neurotrophic factor (CDNF) has shown therapeutic potential in rodent and non-human primate models of Parkinson’s disease by protecting the dopamine neurons from degeneration and even restoring their phenotype and function. Previously, neurorestorative efficacy of CDNF in the 6-hydr...
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doaj-15e75cd83f96494a806ada47fcf6604c2020-11-24T21:30:09ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-06-011310.3389/fnins.2019.00590453317Cerebral Dopamine Neurotrophic Factor Diffuses Around the Brainstem and Does Not Undergo Anterograde Transport After Injection to the Substantia NigraKatrina Albert0Juho-Matti Renko1Kert Mätlik2Mikko Airavaara3Mikko Airavaara4Merja H. Voutilainen5Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, FinlandDivision of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, FinlandInstitute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, FinlandInstitute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, FinlandNeuroscience Center, HiLIFE, University of Helsinki, Helsinki, FinlandInstitute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, FinlandCerebral dopamine neurotrophic factor (CDNF) has shown therapeutic potential in rodent and non-human primate models of Parkinson’s disease by protecting the dopamine neurons from degeneration and even restoring their phenotype and function. Previously, neurorestorative efficacy of CDNF in the 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease as well as diffusion of the protein in the striatum (STR) has been demonstrated and studied. Here, experiments were performed to characterize the diffusion and transport of supra-nigral CDNF in non-lesioned rats. We injected recombinant human CDNF to the substantia nigra (SN) of naïve male Wistar rats and analyzed the brains 2, 6, and 24 h after injections. We performed immunohistochemical stainings using an antibody specific to human CDNF and radioactivity measurements after injecting iodinated CDNF. Unlike the previously reported striatonigral retrograde transport seen after striatal injection, active anterograde transport of CDNF to the STR could not be detected after nigral injection. There was, however, clear diffusion of CDNF to the brain areas surrounding the SN, and CDNF colocalized with tyrosine hydroxylase (TH)-positive neurons. Overall, our results provide insight on how CDNF injected to the SN may act in this region of the brain.https://www.frontiersin.org/article/10.3389/fnins.2019.00590/fullcerebral dopamine neurotrophic factorsubstantia nigraParkinson’s diseasestriatumdiffusiontransport |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Katrina Albert Juho-Matti Renko Kert Mätlik Mikko Airavaara Mikko Airavaara Merja H. Voutilainen |
spellingShingle |
Katrina Albert Juho-Matti Renko Kert Mätlik Mikko Airavaara Mikko Airavaara Merja H. Voutilainen Cerebral Dopamine Neurotrophic Factor Diffuses Around the Brainstem and Does Not Undergo Anterograde Transport After Injection to the Substantia Nigra Frontiers in Neuroscience cerebral dopamine neurotrophic factor substantia nigra Parkinson’s disease striatum diffusion transport |
author_facet |
Katrina Albert Juho-Matti Renko Kert Mätlik Mikko Airavaara Mikko Airavaara Merja H. Voutilainen |
author_sort |
Katrina Albert |
title |
Cerebral Dopamine Neurotrophic Factor Diffuses Around the Brainstem and Does Not Undergo Anterograde Transport After Injection to the Substantia Nigra |
title_short |
Cerebral Dopamine Neurotrophic Factor Diffuses Around the Brainstem and Does Not Undergo Anterograde Transport After Injection to the Substantia Nigra |
title_full |
Cerebral Dopamine Neurotrophic Factor Diffuses Around the Brainstem and Does Not Undergo Anterograde Transport After Injection to the Substantia Nigra |
title_fullStr |
Cerebral Dopamine Neurotrophic Factor Diffuses Around the Brainstem and Does Not Undergo Anterograde Transport After Injection to the Substantia Nigra |
title_full_unstemmed |
Cerebral Dopamine Neurotrophic Factor Diffuses Around the Brainstem and Does Not Undergo Anterograde Transport After Injection to the Substantia Nigra |
title_sort |
cerebral dopamine neurotrophic factor diffuses around the brainstem and does not undergo anterograde transport after injection to the substantia nigra |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2019-06-01 |
description |
Cerebral dopamine neurotrophic factor (CDNF) has shown therapeutic potential in rodent and non-human primate models of Parkinson’s disease by protecting the dopamine neurons from degeneration and even restoring their phenotype and function. Previously, neurorestorative efficacy of CDNF in the 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease as well as diffusion of the protein in the striatum (STR) has been demonstrated and studied. Here, experiments were performed to characterize the diffusion and transport of supra-nigral CDNF in non-lesioned rats. We injected recombinant human CDNF to the substantia nigra (SN) of naïve male Wistar rats and analyzed the brains 2, 6, and 24 h after injections. We performed immunohistochemical stainings using an antibody specific to human CDNF and radioactivity measurements after injecting iodinated CDNF. Unlike the previously reported striatonigral retrograde transport seen after striatal injection, active anterograde transport of CDNF to the STR could not be detected after nigral injection. There was, however, clear diffusion of CDNF to the brain areas surrounding the SN, and CDNF colocalized with tyrosine hydroxylase (TH)-positive neurons. Overall, our results provide insight on how CDNF injected to the SN may act in this region of the brain. |
topic |
cerebral dopamine neurotrophic factor substantia nigra Parkinson’s disease striatum diffusion transport |
url |
https://www.frontiersin.org/article/10.3389/fnins.2019.00590/full |
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