Zusammenfassung
alpha-Synuclein has been reported to be important in modulating brain plasticity and to be a key protein in neurodegenerative diseases, including Lewy body dementia (LBD). We investigated how alpha-synuclein levels modulate adult neurogenesis and the development of dendritic arborization and spines in the dentate gyrus, in which new neurons are constantly added. In the human hippocampus, levels ...
Zusammenfassung
alpha-Synuclein has been reported to be important in modulating brain plasticity and to be a key protein in neurodegenerative diseases, including Lewy body dementia (LBD). We investigated how alpha-synuclein levels modulate adult neurogenesis and the development of dendritic arborization and spines in the dentate gyrus, in which new neurons are constantly added. In the human hippocampus, levels of endogenous alpha-synuclein were increased in LBD, and the numbers of SOX2-positive cells were decreased. We investigated whether newly generated neurons were modulated by endogenous alpha-synuclein, and we found increased adult neurogenesis in alpha/beta-synuclein knock-out mice. In contrast, overexpression of human wild-type alpha-synuclein (WTS) decreased the survival and dendritic development of newborn neurons. Endogenous alpha-synuclein expression levels increased the negative impact of WTS on dendrite development, suggesting a toxic effect of increasing amounts of alpha-synuclein. To attempt a rescue of the dendritic phenotype, we administered rolipram to activate the cAMP response element-binding protein pathway, which led to a partial rescue of neurite development. The current work provides novel insights into the role of alpha-synuclein in adult hippocampal neurogenesis.
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