MANF Promotes Differentiation and Migration of Neural Progenitor Cells with Potential Neural Regenerative Effects in Stroke

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http://hdl.handle.net/10138/233497

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Tseng , K-Y , Anttila , J E , Khodosevich , K , Tuominen , R K , Lindahl , M , Domanskyi , A & Airavaara , M 2018 , ' MANF Promotes Differentiation and Migration of Neural Progenitor Cells with Potential Neural Regenerative Effects in Stroke ' , Molecular therapy , vol. 26 , no. 1 , pp. 238-255 . https://doi.org/10.1016/j.ymthe.2017.09.019

Title: MANF Promotes Differentiation and Migration of Neural Progenitor Cells with Potential Neural Regenerative Effects in Stroke
Author: Tseng, Kuan-Yin; Anttila, Jenni E.; Khodosevich, Konstantin; Tuominen, Raimo K.; Lindahl, Maria; Domanskyi, Andrii; Airavaara, Mikko
Contributor organization: Institute of Biotechnology
Helsinki Institute of Life Science HiLIFE
Faculty of Pharmacy
Division of Pharmacology and Pharmacotherapy
Regenerative pharmacology group
Drug Research Program
Date: 2018-01-03
Language: eng
Number of pages: 18
Belongs to series: Molecular therapy
ISSN: 1525-0016
DOI: https://doi.org/10.1016/j.ymthe.2017.09.019
URI: http://hdl.handle.net/10138/233497
Abstract: Cerebral ischemia activates endogenous reparative processes, such as increased proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) and migration of neural progenitor cells (NPCs) toward the ischemic area. However, this reparative process is limited because most of the NPCs die shortly after injury or are unable to arrive at the infarct boundary. In this study, we demonstrate for the first time that endogenous mesencephalic astrocyte-derived neurotrophic factor (MANF) protects NSCs against oxygen-glucose-deprivation-induced injury and has a crucial role in regulating NPC migration. In NSC cultures, MANF protein administration did not affect growth of cells but triggered neuronal and glial differentiation, followed by activation of STAT3. In SVZ explants, MANF over expression facilitated cell migration and activated the STAT3 and ERK1/2 pathway. Using a rat model of cortical stroke, intracerebroventricular injections of MANF did not affect cell proliferation in the SVZ, but promoted migration of doublecortin (DCX)(+) cells toward the corpus callosum and infarct boundary on day 14 post-stroke. Long-term infusion of MANF into the per'-infarct zone increased the recruitment of DCX+ cells in the infarct area. In conclusion, our data demonstrate a neuroregenerative activity of MANF that facilitates differentiation and migration of NPCs, thereby increasing recruitment of neuroblasts in stroke cortex.
Subject: NEUROTROPHIC FACTOR MANF
ISCHEMIC BRAIN-INJURY
SPINAL-CORD-INJURY
GROWTH-FACTOR
SUBVENTRICULAR ZONE
ADULT NEUROGENESIS
STRIATAL NEUROGENESIS
NEUROBLAST MIGRATION
DOPAMINERGIC-NEURONS
PARKINSONS-DISEASE
1184 Genetics, developmental biology, physiology
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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