Chronic–Progressive Dopaminergic Deficiency Does Not Induce Midbrain Neurogenesis

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 4; p. 775
• Main Authors: Fauser, Mareike, Pan-Montojo, Francisco, Richter, Christian, Kahle, Philipp J., Schwarz, Sigrid C., Schwarz, Johannes, Storch, Alexander, Hermann, Andreas
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.03.2021; MDPI
• Subjects: Acetylcholine receptors (nicotinic); adult neurogenesis; alpha-Synuclein - metabolism; Animal models; Animals; Brain; Cell Proliferation; Disease; Dopamine; Dopamine - deficiency; Dopamine receptors; dopaminergic neurodegeneration; Hindbrain; Humans; Laboratories; Lateral Ventricles - physiology; Mesencephalon; Mesencephalon - physiology; Mice; Mice, Inbred C57BL; Monoclonal antibodies; Movement disorders; Neural stem cells; Neurodegeneration; Neurodegenerative diseases; Neurogenesis; Neurons; non-neurogenic regions; Olfactory bulb; Parkinson's disease; Parkinson´s disease; periventricular regions; Polyclonal antibodies; Receptors, Nicotinic - metabolism; Regeneration; Rhombencephalon - physiology; Stem cells; Subventricular zone; Synuclein; transgenic animal model; Transgenic animals; Ventricle; Ventricle (lateral); Ventricles (cerebral); United States > US; Germany; California; adult neurogenesis; non-neurogenic regions; transgenic animal model; Parkinson´s disease; dopaminergic neurodegeneration; periventricular regions
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10040775

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.