The document discusses the impact of environmental enrichment on various experimental models related to Alzheimer's pathology, emphasizing factors such as animal model type, intervention method, and age. Key findings include reduced amyloidosis and tau hyperphosphorylation in transgenic mice, enhanced cell proliferation in the dentate gyrus, and improved hippocampal long-term potentiation following environmental enrichment. The effects on hippocampal connectivity and cognition-associated signals are also explored.

1. Effects of the environmental model depend on:
1. Experimental (animal) model
2. Type of intervention: enrichment, running, toys etc.
3. Duration
4. Age of animals
5. Gender

2. 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)?

3. 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

4. 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
5
FLAPP
0 0
SH EN SH EN
Tau5 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

5. 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

6. More New Neurons in the dentate gyrus of
APPswe/PS1ΔE9 mice following environmental enrichment
800
* vs. Nontg SH BrdU/NeuN/GFAP
** vs. APP/PS1 SH
BrdU+/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

7. Hippocampal LTP is enhanced following environmental enrichment

8. Does EE affect mainly the
hippocampus?

9. 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