• Media type: E-Article
  • Title: Chronic–Progressive Dopaminergic Deficiency Does Not Induce Midbrain Neurogenesis
  • Contributor: Fauser, Mareike [Author]; Pan-Montojo, Francisco [Author]; Richter, Christian [Author]; Kahle, Philipp J. [Author]; Schwarz, Sigrid C. [Author]; Schwarz, Johannes [Author]; Storch, Alexander [Author]; Hermann, Andreas [Author]
  • imprint: Basel : MDPI, [2023]
  • Language: English
  • Keywords: science-biology ; adult neurogenesis; periventricular regions; non-neurogenic regions; Parkinson´s disease; dopaminergic neurodegeneration; transgenic animal model ; Biologie
  • Origination:
  • Footnote: Hinweis: Link zur Erstveröffentlichung URL: https://doi.org/10.3390/cells10040775
  • Description: 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.
  • Access State: Open Access
  • Rights information: Attribution (CC BY)