Delayed maturation in the middle-aged hippocampus

TRINCHERO MF; SULKES JN; BUTTNER KA; PARDI MB; FONTANET P; SCHINDER AF

Rio de Janeiro, Brasil

Congreso; IBRO LARC World Congress; 2015

International Brain Research Organization

granule cells (DGCs). Aging is one important factor associated to decreased rates of neuronal production. Inrecent studies we have observed that the timing of neuronal maturation is regulated by the activity of thesurrounding networks. In the present work we hypothesize that the middle-aged dentate gyrus may present anenvironment that supports a slow rate of neuronal maturation. To test this hypothesis we injected a retrovirusexpressing GFP in the dentate gyrus of five-month-old mice and analyzed the morphology and expression ofneuronal markers at different ages of the newly born cells. DGCs in middle-aged mice display very immaturefeatures when compared to neurons of the same age in young (two-month-old) mice. Moreover, when neuronsborn in eight-month-old dentate gyrus were analyzed, morphology parameters analysis showed that theseneurons displayed an ever more delayed maturation during the first weeks of their development. This meansthat as the niche gets older, neurons suffer a stronger effect in their maturation rate. Loose patch experimentsproved that these neurons are connected to the network when they are 6 weeks old. We explored then,different factors that could modulate the rate of maturation of DGCs born in an aged hippocampus. Runningreversed the effects of aging on neurons born in middle-aged mice. Next we asked if increasing the intrinsicactivity of the cell would accelerate maturation of neurons born in five-month-old mice. By using receptorsactivated solely by synthetic ligands (RASSLs) we increased 21-day-old neurons activity born in five-month-oldmice causing an acceleration of their maturation. We are now exploring whether neurotrophic factors representan important feature in terms of maturation of neurons born in the middle-age hippocampus given that they areknown to be decreased in aging mice.