Effects of the environmental model depend on:1. Experimental (animal) model2. Type of intervention: enrichment, running, toys etc.3. Duration4. Age of animals5. Gender
Environmental Enrichment:1. Multiple effects= multiple signaling pathways?1. If multiple pathways- do they all lead to the same downstream effect?3. If not, how do we identify the critical signal(s)?
Amelioration of pathology: Reduced amyloidosis in FAD transgenic mice following an enriched environment Standard Housing Enriched Hippocampus Cortex Cortex Hippocampus 25 Relative level (Arbitrary Units) Relative level (Arbitrary Units) 25 20 20 15 * 15 ** 10 10 5 5 0 0 Standard Housing Enriched Standard Housing Enriched
Amelioration of pathology: Reduced tau hyperphosphorylation in FAD transgenic mice following an enriched environment 25 20 FL-APP (Arbitrary Units) Tau5 (Arbitrary Units) Hippocampus 20 15 15 Standard Housing Enriched 10 10 5 5FLAPP 0 0 SH EN SH ENTau5 40 40 PHF1 (Arbitrary Units) KHC (Arbitrary Units) 30 30 PHF1 20 20 KLC 10 10 0 0 KHC SH EN SH EN 30 20 Actin (Arbitrary Units) Actin KLC (Arbitrary Units) 15 20 10 10 5 0 0 SH EN SH EN
Enhanced Cell Proliferation and neuronal differentiation in the dentate gyrus of APPswe/PS1ΔE9 mice following environmental enrichment * vs. nonTg SH Standard Housing Enrichment 8000 ** vs. APP/PS1 SH * NonTg Total BrdU+ cells 6000 ** 4000 APPSwe/PS1ΔE9 2000 0 NonTg APP/PS1 * vs. nonTg SH Standard Housing 4000 ** vs. APP/PS1 SH Enriched BrdU/DCX * ** BrdU+/DCX+ cells 3000 2000 1000 0 NonTg APP/PS1
More New Neurons in the dentate gyrus of APPswe/PS1ΔE9 mice following environmental enrichment 800 * vs. Nontg SH BrdU/NeuN/GFAP ** vs. APP/PS1 SHBrdU+/NeuN+ cells ** 600 * 400 200 0 NonTg APP/PS1 * vs. nonTg SH Standard Housing 500 ** vs. APP/PS1 SH Enriched * ** BrdU/GFAP BrdU/S100β BrdU+/GFAP+ cells 400 300 200 100 0 NonTg APP/PS1
Hippocampal LTP is enhanced following environmental enrichment
Increased connectivity between CA1 and cortical areas in FAD-linked mice Following environmental enrichment Regions that correlated with the extracted time-course from left CA1 and right CA1 for each individual animal. Spin echo anatomical reference T1 weighted images acquired in the coronal plane. Molecularly mediated by cognition-associated signals Little, Foxely and Lazarov, J Alz Dis, 2012