Combination of CDNF and Deep Brain Stimulation Decreases Neurological Deficits in Late-stage Model Parkinson's Disease

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Huotarinen , A , Penttinen , A-M , Bäck , S , Voutilainen , M H , Julku , U , Piepponen , T P , Männistö , P T , Saarma , M , Tuominen , R , Laakso , A & Airavaara , M 2018 , ' Combination of CDNF and Deep Brain Stimulation Decreases Neurological Deficits in Late-stage Model Parkinson's Disease ' , Neuroscience , vol. 374 , pp. 250-263 . https://doi.org/10.1016/j.neuroscience.2018.01.052

Title: Combination of CDNF and Deep Brain Stimulation Decreases Neurological Deficits in Late-stage Model Parkinson's Disease
Author: Huotarinen, Antti; Penttinen, Anna-Maija; Bäck, Susanne; Voutilainen, Merja H.; Julku, Ulrika; Piepponen, T. Petteri; Männistö, Pekka T.; Saarma, Mart; Tuominen, Raimo; Laakso, Aki; Airavaara, Mikko
Other contributor: University of Helsinki, Neurokirurgian yksikkö
University of Helsinki, Institute of Biotechnology
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Institute of Biotechnology
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Institute of Biotechnology
University of Helsinki, Faculty of Pharmacy
University of Helsinki, HUS Neurocenter
University of Helsinki, Institute of Biotechnology













Date: 2018-03-15
Language: eng
Number of pages: 14
Belongs to series: Neuroscience
ISSN: 0306-4522
DOI: https://doi.org/10.1016/j.neuroscience.2018.01.052
URI: http://hdl.handle.net/10138/233649
Abstract: Several neurotrophic factors ( NTF) are shown to be neuroprotective and neurorestorative in pre-clinical animal models for Parkinson's disease ( PD), particularly in models where striatal dopamine neuron innervation partially exists. The results of clinical trials on late-stage patients have been modest. Subthalamic deep brain stimulation ( STN DBS) is a proven treatment for a selected group of advanced PD patients. The cerebral dopamine neurotrophic factor ( CDNF) is a promising therapeutic protein, but its effects in animal models of late-stage PD have remained under-researched. The interactions of NTF and STN DBS treatments have not been studied before. We found that a nigral CDNF protein alone had only a marginal effect on the behavioral deficits in a late-stage hemiparkinsonian rat model ( 6-OHDA MFB). However, CDNF improved the effect of acute STN DBS on front limb use asymmetry at 2 and 3 weeks after CDNF injection. STN lesion-modeling chronic stimulation-had an additive effect in reducing front limb use in the cylinder test and apomorphine-induced rotation. The combination of CDNF and acute STN DBS had a favorable effect on striatal tyrosine hydroxylase. This study presents a novel additive beneficial effect of NTF and STN DBS, which might be explained by the interaction of DBS-induced endogenous NTFs and exogenously injected CDNF. SNpc can be reached via similar trajectories used in clinical STN DBS, and this interaction is an important area for future studies. (C) 2018 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).
Subject: CDNF
MANF
GDNF
neurotrophic factor
median forebrain bundle
6-hydroxydopamine
STN DBS
HIGH-FREQUENCY STIMULATION
SUBTHALAMIC NUCLEUS STIMULATION
NIGROSTRIATAL DOPAMINE SYSTEM
6-HYDROXYDOPAMINE LESIONED RATS
NEURONS IN-VIVO
NEUROTROPHIC FACTOR
GENE-THERAPY
STRIATAL DOPAMINE
MICE
3112 Neurosciences
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