Abstract
Epidemiological studies indicate that intellectual activity prevents or delays the onset of Alzheimer's disease (AD). Similarly, cognitive stimulation using environmental enrichment (EE), which increases adult neurogenesis and functional integration of newborn neurons into neural circuits of the hippocampus, protects against memory decline in transgenic mouse models of AD, but the mechanisms involved are poorly understood. To study the therapeutic benefits of cognitive stimulation in AD we examined the effects of EE in hippocampal neurogenesis and memory in a transgenic mouse model of AD expressing the human mutant β-amyloid (Aβ) precursor protein (APPSw,Ind). By using molecular markers of new generated neurons (bromodeoxiuridine, NeuN and doublecortin), we found reduced neurogenesis and decreased dendritic length and projections of doublecortin-expressing cells of the dentate gyrus in young APPSw,Ind transgenic mice. Moreover, we detected a lower number of mature neurons (NeuN positive) in the granular cell layer and a reduced volume of the dentate gyrus that could be due to a sustained decrease in the incorporation of new generated neurons. We found that short-term EE for 7 weeks efficiently ameliorates early hippocampal-dependent spatial learning and memory deficits in APPSw,Ind transgenic mice. The cognitive benefits of enrichment in APPSw,Ind transgenic mice were associated with increased number, dendritic length and projections to the CA3 region of the most mature adult newborn neurons. By contrast, Aβ levels and the total number of neurons in the dentate gyrus were unchanged by EE in APPSw,Ind mice. These results suggest that promoting the survival and maturation of adult generated newborn neurons in the hippocampus may contribute to cognitive benefits in AD mouse models.
Highlights
Adult neurogenesis is a continuous physiological process that occurs in the dentate gyrus (DG) of the hippocampus and the subventricular zone in rodents and primates, including humans [1,2,3,4]
APPSw,Ind transgenic mice show hippocampal-dependent learning and memory deficits associated with accumulation of intraneuronal Ab in the DG, CA1 and CA3 hippocampal regions at 6 months of age [40,42]
We evaluated the effects of short-term EE in APPSw,Ind mice at 4 months, an age characterized by subtle spatial memory deficits and increased hippocampal levels of Ab but prior to amyloid deposition [39,42,68]
Summary
Adult neurogenesis is a continuous physiological process that occurs in the dentate gyrus (DG) of the hippocampus and the subventricular zone in rodents and primates, including humans [1,2,3,4]. During the critical maturation stage (1–4 weeks), newborn neurons undergo dendritic morphological changes, project their axons to the CA3 region and integrate functionally into hippocampal neural circuits [8,9,10,11]. There is strong evidence indicating that adult neurogenesis contributes to hippocampal-dependent learning and memory [9,12,13,14,15]. Activity-induced stimulation and morphological changes of newborn immature neurons during the maturation stage are critical for their functional integration into hippocampal memory circuits [9,12,15,20]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
