Chronic-Progressive Dopaminergic Deficiency Does Not Induce Midbrain Neurogenesis.

Autor: Fauser M; Department of Neurology, University Medical Center Rostock, 18147 Rostock, Germany.; Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany., Pan-Montojo F; Munich Cluster for Systems Neurology, Department of Psychiatry, University Hospital LMU, 80336 Munich, Germany., Richter C; Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany., Kahle PJ; Laboratory of Functional Neurogenetics, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, 72076 Tübingen, Germany.; German Centre for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany., Schwarz SC; Department of Neurology, University Hospital Leipzig, 04103 Leipzig, Germany., Schwarz J; Department of Neurology, University Hospital Leipzig, 04103 Leipzig, Germany.; Department of Neurology, Klinik Haag i. OB, 83527 Oberbayern, Germany., Storch A; Department of Neurology, University Medical Center Rostock, 18147 Rostock, Germany.; Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.; German Centre for Neurodegenerative Diseases (DZNE) Rostock-Greifswald, 18147 Rostock, Germany.; Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany., Hermann A; Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.; German Centre for Neurodegenerative Diseases (DZNE) Rostock-Greifswald, 18147 Rostock, Germany.; Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany.; Translational Neurodegeneration Section 'Albrecht Kossel', Department of Neurology, University Medical Center Rostock, 18147 Rostock, Germany.
Jazyk: angličtina
Zdroj: Cells [Cells] 2021 Mar 31; Vol. 10 (4). Date of Electronic Publication: 2021 Mar 31.
DOI: 10.3390/cells10040775
Abstrakt: Background: Consecutive adult neurogenesis is a well-known phenomenon in the ventricular-subventricular zone of the lateral wall of the lateral ventricles (V-SVZ) and has been controversially discussed in so-called "non-neurogenic" brain areas such as the periventricular regions (PVRs) of the aqueduct and the fourth ventricle. Dopamine is a known modulator of adult neural stem cell (aNSC) proliferation and dopaminergic neurogenesis in the olfactory bulb, though a possible interplay between local dopaminergic neurodegeneration and induction of aNSC proliferation in mid/hindbrain PVRs is currently enigmatic.
Objective/hypothesis: To analyze the influence of chronic-progressive dopaminergic neurodegeneration on both consecutive adult neurogenesis in the PVRs of the V-SVZ and mid/hindbrain aNSCs in two mechanistically different transgenic animal models of Parkinson´s disease (PD).
Methods: We used Thy1-m[A30P]h α synuclein mice and Leu9'Ser hypersensitive α4* nAChR mice to assess the influence of midbrain dopaminergic neuronal loss on neurogenic activity in the PVRs of the V-SVZ, the aqueduct and the fourth ventricle.
Results: In both animal models, overall proliferative activity in the V-SVZ was not altered, though the proportion of B2/activated B1 cells on all proliferating cells was reduced in the V-SVZ in Leu9'Ser hypersensitive α4* nAChR mice. Putative aNSCs in the mid/hindbrain PVRs are known to be quiescent in vivo in healthy controls, and dopaminergic deficiency did not induce proliferative activity in these regions in both disease models.
Conclusions: Our data do not support an activation of endogenous aNSCs in mid/hindbrain PVRs after local dopaminergic neurodegeneration. Spontaneous endogenous regeneration of dopaminergic cell loss through resident aNSCs is therefore unlikely.
Databáze: MEDLINE
Externí odkaz: