A team of researchers from Cnr-Ibbc Italy has identified the anti-neural aging role played by this molecule in vivo. The results are published in Frontiers in Cell and Developmental Biology
The mammalian brain continues to generate neurons throughout life, starting from neural stem cells, in two specific areas called neurogenic niches: the dentate gyrus of the hippocampus and the subventricular area.
A team from the Institute of Biochemistry and Cell Biology of the Italian National Research Council (Cnr-Ibbc), led by Felice Tirone and Laura Micheli in collaboration with Giorgio D'Andrea and Manuela Ceccarelli, sought to identify genes particularly involved in maintaining the production of neurons during aging.
For this purpose, the researchers used an in vivo aging model, with reduced production of stem cells and neurons of the dentate gyrus of the hippocampus, and consequent reduction of memory capacity. In fact, neurogenesis in the dentate gyrus is particularly important for the formation of associative memory, which allows different memories to be linked together. Both neurogenesis and memory are reduced during aging and neurodegenerative diseases. "Through a genomic analysis, we identified in this model genes that were reactivated by voluntary running, which we know to be a powerful stimulus for the production of neurons," explains Tirone. “In particular, we observed that alpha-synuclein - a gene whose expression is greatly reduced in our model and also in physiological aging - is brought back to normal levels by running. Furthermore, if alpha-synuclein reduced expression in the aged dentate gyrus is artificially increased, then stem cells restart to produce neurons ”. The evidence is therefore that alpha-synuclein plays a key role in maintaining neuron production in the aging brain. "It is also known that in the case of an excess of alpha-synuclein levels or when its structure is altered, this triggers a process of neurodegeneration, in particular in synucleinopathies, including for example Parkinson's disease. Our work therefore sheds light on the physiological function of this molecule and highlights it as a possible target for therapies in the elderly, preventive of neurodegeneration ”, concludes Micheli.
Contributing to the study, for the analysis of genomic data, were Teresa Maria Creanza and Nicola Ancona of the Institute of intelligent industrial systems and technologies for advanced manufacturing (Cnr-Stiima), Roberto Coccurello of the Institute of complex systems (Cnr-Isc ) and Fondazione Santa Lucia IRCCS and Giacomo Giacovazzo of the University of Rome Tor Vergata for the induction of cerebral expression of alpha-synuclein, and Raffaella Scardigli, of the Institute of Translational Pharmacology (Cnr-Ift) for gene expression studies .
Who: Inst of Biochemistry and cell biology of Consiglio nazionale delle ricerche, Cnr-Ibbc, Rome Italy
What: Micheli L, Creanza TM, Ceccarelli M, D'Andrea G, Giacovazzo G, Ancona N, Coccurello R, Scardigli R, Tirone F. (2021). Transcriptome Analysis in a Mouse Model of Premature Aging of Dentate Gyrus: Rescue of Alpha-Synuclein Deficit by Virus-Driven Expression or by Running Restores the Defective Neurogenesis. Front Cell Dev Biol. 9:696684, https://doi.org/10.3389/fcell.2021.696684
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