Decreased long-term survival of new neurons in the aged hippocampus.
1. Behavioral and Cognitive, UNAM INB, Juriquilla, Mexico;
2. ARL NSMA
3. Evelyn F. McKnight Brain Inst., Univ. Arizona, Tucson, AZ
Adult neurogenesis is a key mechanism of structural plasticity in the hippocampal dentate gyrus, a subregion that is particularly susceptible to the effects of advancing age (Small et al., 2004). In young animals, newly generated neurons are functionally integrated in to the hippocampal network that responds to behavioral exploration by expressing the immediate-early gene Arc, a reliable reporter of activity in individual neurons, when tested 5 months later (Ramirez-Amaya et al., 2006). Moreover, newly-generated granule cells are far more likely to become part of the neuronal ensemble responding to spatial processing than older granule cells. Although the proliferation of new neurons in the adult brain is known to decline during aging (e.g., Kuhn et al., 1996), the degree to which neurons generated in senescence retain the capacity to functionally integrate into dentate networks remains unknown. To address this question, young (9 months) and aged (22 months old) rats were injected with BrdU (50mg/kg) daily for 5 days. Following a four month delay, animals were sacrificed 60 minutes after a single 5 min exploration in a novel environment. The tissue was then analyzed using triple immunohistochemistry (NeuN, Arc and BrdU) combined with high-resolution confocal microscopy. A lower number of new neurons (i.e., BrdU+) are present in aged animals relative to their young counterparts, consistent with previous studies. The ability of the reduced population of newly-born granule cells to functionally integrate into behaviorally-relevant neuronal networks, however, remains to be determined.
Grant/Other Support: AG009219; McKnight Brain Research Foundation; state of Arizona and ADHS; DGAPA-UNAM IN 213907
Keyword (Complete): granule cells; Arc; neurogenesis; BrdU