Lindahl , M , Chalazonitis , A , Palm , E , Pakarinen , E , Danilova , T , Pham , T D , Setlik , W , Rao , M , Voikar , V , Huotari , J , Kopra , J , Andressoo , J-O , Piepponen , P T , Airavaara , M , Panhelainen , A , Gershon , M D & Saarma , M 2020 , ' Cerebral dopamine neurotrophic factor-deficiency leads to degeneration of enteric neurons and altered brain dopamine neuronal function in mice ' , Neurobiology of Disease , vol. 134 , 104696 . https://doi.org/10.1016/j.nbd.2019.104696
Title: | Cerebral dopamine neurotrophic factor-deficiency leads to degeneration of enteric neurons and altered brain dopamine neuronal function in mice |
Author: | Lindahl, Maria; Chalazonitis, Alcmene; Palm, Erik; Pakarinen, Emmi; Danilova, Tatiana; Pham, Tuan D.; Setlik, Wanda; Rao, Meenakshi; Voikar, Vootele; Huotari, Jatta; Kopra, Jaakko; Andressoo, Jaan-Olle; Piepponen, Petteri T.; Airavaara, Mikko; Panhelainen, Anne; Gershon, Michael D.; Saarma, Mart |
Contributor organization: | Helsinki One Health (HOH) Staff Services Institute of Biotechnology Division of Pharmacology and Pharmacotherapy Medicum Regenerative pharmacology group Drug Research Program Timo Petteri Piepponen / Principal Investigator University Management Neuroscience Center Mart Saarma / Principal Investigator |
Date: | 2020-02 |
Language: | eng |
Number of pages: | 18 |
Belongs to series: | Neurobiology of Disease |
ISSN: | 0969-9961 |
DOI: | https://doi.org/10.1016/j.nbd.2019.104696 |
URI: | http://hdl.handle.net/10138/311630 |
Abstract: | Cerebral dopamine neurotrophic factor (CDNF) is neuroprotective for nigrostriatal dopamine neurons and restores dopaminergic function in animal models of Parkinson's disease (PD). To understand the role of CDNF in mammals, we generated CDNF knockout mice (Cdnf(-/-)), which are viable, fertile, and have a normal life-span. Surprisingly, an age-dependent loss of enteric neurons occurs selectively in the submucosal but not in the myenteric plexus. This neuronal loss is a consequence not of increased apoptosis but of neurodegeneration and autophagy. Quantitatively, the neurodegeneration and autophagy found in the submucosal plexus in duodenum, ileum and colon of the Cdnf(-/-) mouse are much greater than in those of Cdnf(+/+) mice. The selective vulnerability of submucosal neurons to the absence of CDNF is reminiscent of the tendency of pathological abnormalities to occur in the submucosal plexus in biopsies of patients with PD. In contrast, the number of substantia nigra dopamine neurons and dopamine and its metabolite concentrations in the striatum are unaltered in Cdnf(-/-) mice; however, there is an age-dependent deficit in the function of the dopamine system in Cdnf(-/-) male mice analyzed. This is observed as D-amphetamine-induced hyperactivity, aberrant dopamine transporter function, and as increased D-amphetamine-induced dopamine release demonstrating that dopaminergic axon terminal function in the striatum of the Cdnf(-/-) mouse brain is altered. The deficiencies of Cdnf(-/-) mice, therefore, are reminiscent of those seen in early stages of Parkinson's disease. |
Subject: |
Cerebral dopamine neurotrophic factor (CDNF)
Knockout mouse Enteric nervous system Midbrain Dopaminergic Dopamine transporter Neurodegeneration Autophagy Parkinson's disease UNFOLDED PROTEIN RESPONSE FLUORO-JADE-C PARKINSONS-DISEASE NERVOUS-SYSTEM ENDOPLASMIC-RETICULUM ALPHA-SYNUCLEIN CDNF PROTECTS CELL-DEATH ER STRESS MANF 3112 Neurosciences |
Peer reviewed: | Yes |
Rights: | cc_by_nc_nd |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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