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Thesis

English

ID: <

10670/1.fv77ak

>

Where these data come from
Regulation of cell fate during postnatal neurogenesis : role of dopaminergic innervation from the midbrain

Abstract

In the postnatal and adult mammalian brain neurogenesis persists in the subgranular zone of the hippocampal dentate gyrus and the subventricular zone (SVZ). In the SVZ slowly dividing stem cells give rise to neuroblasts that migrate to the olfactory bulb (OB) where they reach the granule and glomerular cell layer of the OB and differentiate into different interneuron subtypes including a small fraction of dopaminergic interneurons. The discovery of postnatal and adult neurogenesis has changed the view of the plasticity of the brain remarkably and raised the hope for new therapeutical approaches in the field of neurodegenerative diseases. Since in Parkinson’s disease the main motor symptoms are caused by the dopaminergic denervation of the striatum adjacent to SVZ, the understanding of the generation and differentiation of OB dopaminergic neurons has received special attention. Interestingly, the neurotransmitter dopamine itself has been suggested to influence olfactory bulb neurogenesis via direct innervation of SVZ by midbrain dopaminergic neurons. However, data on this topic have been contradictory. In this study, I investigated how dopaminergic innervation influences SVZ neurogenesis and the fate of SVZ progenitors. I combined a 6-OHDA model of dopaminergic denervation in postnatal mice with in vivo forebrain electroporation to specifically label lateral and dorsal SVZ progenitors and to follow their fate in the olfactory bulb.

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