Cerebral dopamine neurotrophic factor-deficiency leads to degeneration of enteric neurons and altered brain dopamine neuronal function in mice

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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: University of Helsinki, Helsinki One Health (HOH)
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Division of Pharmacology and Pharmacotherapy
University of Helsinki, Medicum
University of Helsinki, Regenerative pharmacology group
University of Helsinki, Neuroscience Center
University of Helsinki, Helsinki One Health (HOH)
University of Helsinki, Mart Saarma / Principal Investigator
Date: 2020-02
Language: eng
Number of pages: 18
Belongs to series: Neurobiology of Disease
ISSN: 0969-9961
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
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