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bioRxiv · 10.1101/419382

Deciphering defective subventricular adult neurogenesis in cyclin D2-deficient mice

Płatek, R.·Kaczmarek, L.·Czupryn, A.
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Abstract

Adult neurogenesis occurring in the brain of adult mammals is considered to have potential therapeutical applications. New neurons are produced constitutively from postnatal neural stem cells/precursors residing in two neurogenic regions: the subventricular zone (SVZ) of the lateral ventricles and the subgranular layer in the dentate gyrus of the hippocampus. Newly-generated neuroblasts from the SVZ migrate long distance towards the olfactory bulb and repopulate different subtypes of inhibitory interneurons modulating the olfactory processing. It was reported that cyclin D2 knockout mice (cD2-KO) present reduced generation of new hippocampal neurons, however proliferation deficiency and mechanisms responsible for dysregulation of subventricular precursors, derived progenitors, and olfactory interneurons need to be detaily investigated. In this report, proliferative activity of different subpopulations of SVZ neural precursors, cell migration, and differentiation in cD2-KO mice was characterized. For that goal, EdU, a thymidine analogue, proliferation mapping combined with multi-epitope immunohisto-chemical detection of endogenous stage-specific cell markers was carried out. Severely reduced number of newly-generated cells in the subventricular niche was demonstrated that was not accompanied by increased level of apoptotic death. Surprisingly, the number of B1 quiescent precursor subpopulation was not affected, whereas the number of B1 type active primary precursors, intermediate/transiently-amplifying progenitors (C type cells), and neuroblasts (A type cells) were reduced. The analyses suggest that cycline D2 might be critical for transition of B1 precursor quiescent cells into B1 active cells. We also demonstrate that the subpopulation of calbindin interneurons is reduced in the olfactory bulb. Deciphering processes underlying a potential modulation of intensity of adult neurogenesis at the cellular levels could lead to replacement therapies after injury, stroke, or neurodegenerative disease in the central nervous system.

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Płatek, R., Kaczmarek, L., Czupryn, A.. 2018-09-17. Deciphering defective subventricular adult neurogenesis in cyclin D2-deficient mice. https://doi.org/10.1101/419382

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