Anne Schwerk1, Jennifer Altschüler1, Manfred Roch2, Manfred Gossen3, Christine Winter4, Jürgen Berg1, Andreas Kurtz5, Barbara Steiner6. 1. Department of Neurology, Charité University Medicine, Berlin, Germany. 2. Berlin-Brandenburg Centre for Regenerative Therapies, Charité University Medicine, Berlin, Germany. 3. Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany. 4. Department of Psychiatry, Technical University Dresden, Dresden, Germany. 5. Berlin-Brandenburg Centre for Regenerative Therapies, Charité University Medicine, Berlin, Germany; Seoul National University, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul, Republic of Korea. 6. Department of Neurology, Charité University Medicine, Berlin, Germany. Electronic address: barbara.steiner@charite.de.
Abstract
BACKGROUND AIMS: In Parkinson's disease (PD), neurogenesis in the subventricular zone (SVZ)-olfactory bulb (OB) axis is affected as the result of the lack of dopaminergic innervations reaching the SVZ. This aberrant network has been related to the hyposmia of PD patients, which is an early diagnostic marker of the disease. Consequently, much interest arose in finding mechanisms to modulate the SVZ-OB axis. Direct modulation of this axis could be achieved by transplantation of mesenchymal stromal cells (MSC), as it has been shown in rat and mouse PD models. However, the neurogenic effect of MSC in PD was thus far only analyzed weeks after transplantation, and little is known about effects immediately after transplantation. METHODS: We assessed the acute neuroprotective and neurogenic effects of adipose-derived MSC transplanted into the rat substantia nigra in the 6-hydroxydopamine model of PD. RESULTS: Three days after transplantation, subventricular neurogenesis was significantly increased in MSC-transplanted versus non-transplanted animals. Most MSC were found in the region of the substantia nigra and the surrounding arachnoid mater, expressing S100β and brain-derived neurotrophic factor, whereas some MSC showed an endothelial phenotype and localized around blood vessels. CONCLUSIONS: The acute neurogenic effects and neurotrophic factor expression of MSC could help to restore the SVZ-OB axis in PD.
BACKGROUND AIMS: In Parkinson's disease (PD), neurogenesis in the subventricular zone (SVZ)-olfactory bulb (OB) axis is affected as the result of the lack of dopaminergic innervations reaching the SVZ. This aberrant network has been related to the hyposmia of PDpatients, which is an early diagnostic marker of the disease. Consequently, much interest arose in finding mechanisms to modulate the SVZ-OB axis. Direct modulation of this axis could be achieved by transplantation of mesenchymal stromal cells (MSC), as it has been shown in rat and mousePD models. However, the neurogenic effect of MSC in PD was thus far only analyzed weeks after transplantation, and little is known about effects immediately after transplantation. METHODS: We assessed the acute neuroprotective and neurogenic effects of adipose-derived MSC transplanted into the rat substantia nigra in the 6-hydroxydopamine model of PD. RESULTS: Three days after transplantation, subventricular neurogenesis was significantly increased in MSC-transplanted versus non-transplanted animals. Most MSC were found in the region of the substantia nigra and the surrounding arachnoid mater, expressing S100β and brain-derived neurotrophic factor, whereas some MSC showed an endothelial phenotype and localized around blood vessels. CONCLUSIONS: The acute neurogenic effects and neurotrophic factor expression of MSC could help to restore the SVZ-OB axis in PD.
Authors: Ana Isabel Sánchez-Castillo; M Rosario Sepúlveda; José Luis Marín-Teva; Miguel A Cuadros; David Martín-Oliva; Elena González-Rey; Mario Delgado; Veronika E Neubrand Journal: Biomolecules Date: 2022-01-27